Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Epidermal Growth Factor”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMedDate not supplied

Epidermal growth factor, epidermal growth factor receptors, intestinal growth, and adaptation.

Epidermal growth factor (EGF) is an important constituent of several gastrointestinal secretions. Many studies in both animals and humans have shown EGF to have multiple effects upon gut epithelial cells. These include cytoprotection, stimulatory effects on cell proliferation and migration, induction of gene expression such as mucosal enzymes and trefoil proteins, and inhibitory effects on gastric acid secretion. The main conundrum associated with EGF action is the disparity between experimental studies on its luminal and systemic actions. Opinion is sharply divided as to whether or not EGF has any action when given luminally and on the site of the EGF receptors on gut epithelial cells. Most studies agree that the EGF receptors are located on the basolateral surface, in which case EGF should only be active if surface ulceration has occurred--unless there is translocation across the epithelium. There are several clinical situations in which EGF might be useful in cytoprotection and in stimulating repair and regeneration in the gut. These include necrotizing enterocolitis and mucositis, and it is to be hoped that the solid basis of experimental studies on EGF might stimulate work on this topic.

Animals↗
PubMed1993

[Immunohistochemical study in acquired cystic disease of the kidney--expression of vimentin, epidermal growth factor, epidermal growth factor receptor and c-erb B2 gene product].

Acquired cystic disease of the kidney (ACDK) reveals abnormal epithelial cell growth which suggests a cotinuum of cyst, adenoma and renal cell carcinoma (RCC). In the present study, we examined potential role of vimentin and growth factors for cyst growth and proliferation in 20 cases with ACDK by immunoperoxidase staining method. 1281 cysts with single-layered epithelia and 89 cysts with multi-layered epithelia (atypical cyst) were studied. Intermediated filament, vimentin was positive in staining in 41.6% of cysts with single-layered epithelia, in 73.1% of cyst with multi-layered epithelia and in 100% of adenomas and RCCs. Vimentin expression, therefore, may be considered as an indication of cellular differentiation among proliferating tubular or intracystic cells. In order to evaluate the growth and/or proliferative capabilities of cyst epithelia, epidermal growth factor (EGF), epidermal growth factor receptor (EGFR) and c-erb B2 gene product were determined in cyst epithelia, adenoma and adenocarcinoma. EGF showed positive staining in 49.1% of cyst with single-layered epithelia, in 68.4% of cyst with multi-layered epithelia, in 2 of 3 adenomas and in 5 of 8 RCCs. EGFR expression was observed in 61.7% of cyst with single-layered epithelia, in 94.7% of cyst with multi-layered epithelia, in 100% of adenomas and RCCs. Co-expression of EGF and EGFR was observed in 40.3% of cyst with single-layered epithelia and in 67.1% of cyst with multi-layered epithelia. C-erb B2 gene product was positive in 9.7% of cyst with single-layered epithelia, in 100% of cyst with multi-layered epithelia and in 3 of 7 RCCs. These findings indicate that the expression of vimentin and overexpression of these growth factors and receptors appear to be one of the mechanisms operating in potentiating the abnormal growth of cyst epithelia, including potential for oncogenesis of RCC.

Adolescent↗
PubMed1992

The immunohistochemical expressions of epidermal growth factors, epidermal growth factor receptors and c-erbB-2 oncoprotein in human pancreatic cancer.

The expressions of epidermal growth factors (EGF), epidermal growth factor receptors (EGFR), and the c-erbB-2 oncoprotein were immunohistochemically examined in 25 cases of human pancreatic carcinoma and epineoplastic pancreatitis and in 10 non-cancerous/non-inflammatory pancreatic tissues. The positive rates of EGF, EGFR, and the c-erbB-2 oncoprotein in cancer tissues were 72%, 36%, and 28%, respectively. EGF was stained mainly in the cytoplasm and partly on the surfaces of the cancer cells. EGFR and the c-erbB-2 oncoprotein were stained mainly on the surfaces of the cancer cells and partly in the cytoplasm. The expressions of these 3 products correlated significantly with tumor invasion into the anterior and posterior areas surrounding the pancreas. In the EGF, EGFR, and c-erbB-2 positive cancer tissues, some stromal cells, that is fibroblasts and endothelial cells, were also positive. In the adjacent pancreatic tissues with inflammation, these products were noted in some ductal cells, acinar cells, fibroblasts and endothelial cells. No distinct staining was detected in non-cancerous/non-inflammatory tissues. The survival period for patients who tested positive for these three proteins was statistically shorter than for those who tested negative. These results suggest that the coexpression of EGF and EGFR and the expression of the c-erbB-2 oncoprotein are related to the existence of the invasion of human pancreatic cancer. Furthermore, an immunohistochemical examination of these three products is useful in forming a prognosis for pancreatic cancer patients.

Epidermal Growth Factor↗
PubMed2005

rab7 activity affects epidermal growth factor:epidermal growth factor receptor degradation by regulating endocytic trafficking from the late endosome.

The epidermal growth factor receptor (EGFR) is a member of the receptor tyrosine kinase family. Ligand (epidermal growth factor or EGF) binding to the EGFR results in the coordinated activation and integration of biochemical signaling events to mediate cell growth, migration, and differentiation. One mechanism the cell utilizes to orchestrate these events is ligand-mediated endocytosis through the canonical clathrin-mediated endocytic pathway. Identification of proteins that regulate the intracellular movement of the EGF.EGFR complex is an important first step in dissecting how specificity of EGFR signaling is conferred. We examined the role of the small molecular weight guanine nucleotide-binding protein (G-protein) rab7 as a regulator of the distal stages of the endocytic pathway. Through the transient expression of activating and inactivating mutants of rab7 in HeLa cells, we have determined that rab7 activity directly correlates with the rate of radiolabeled EGF and EGFR degradation. Furthermore, when inhibitory mutants of rab7 are expressed, the internalized EGF.EGFR complex accumulates in high-density endosomes that are characteristic of the late endocytic pathway. Thus, we conclude that rab7 regulates the endocytic trafficking of the EGF.EGFR complex by regulating its lysosomal degradation.

Adenoviridae↗
PubMed1996

Expression of epidermal growth factor, epidermal growth factor receptor and transforming growth factor-alpha in the human fetal inner ear.

The expression of epidermal growth factor (EGF), EGF receptor and transforming growth factor (TGF)-alpha was analyzed in the human fetal inner ear using immuno-histochemical methods. EGF receptor was observed only in 9.5-week-old fetal vestibular epithelia. In 14- and 16-week-old fetuses, EGF receptor could not be detected. TGF-alpha was observed strongly in the 9- and 11-week-old vestibular epithelia, whereas only trace amounts were detectable in the 14- and 16-week-old vestibular epithelia. These findings suggest that EGF and TGF-alpha probably have a mitogenic effect in the sensory epithelia of the fetal inner ear, especially at early stages of development.

Ear, Inner↗
PubMed1996

Epidermal growth factor, epidermal growth factor receptor, and transforming growth factor-alpha in human hyperplastic prostate tissue: expression and cellular localization.

It is widely accepted that polypeptide growth factors are involved in the growth and development of normal and neoplastic human prostate. It has been previously reported that epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) receptors are present in the human hyperplastic prostate tissue (BPH). To add information on the mechanism of action of EGF and transforming growth factor-alpha (TGF alpha), a peptide correlated to EGF, and the EGF receptor (EGF-R) in the human prostate, we studied the expression and cellular localization of messenger ribonucleic acid (RNA) encoding EGF, EGF-R, and TGF alpha in BPH tissue. Reverse transcriptase-PCR of total RNA extracted from BPH tissues documented the presence of specific transcripts for EGF, EGF-R, and TGF alpha. In situ hybridization with specific RNA probes synthesized from the respective complementary DNA demonstrated that EGF, EGF-R, and TGF alpha messenger RNAs were mainly localized in the epithelial cells. Immunprecipitation and Western blot analysis showed that BPH tissue contained the corresponding proteins, EGF and TGF alpha. Our findings provide additional support for the idea that EGF and TGF alpha may be considered specialized symbols in the language of cell-cell interactions and for the hypothesis that in the human prostate they seem to act in an autocrine fashion.

Epidermal Growth Factor↗
PubMed2002

Modeling the epidermal growth factor -- epidermal growth factor receptor l2 domain interaction: implications for the ligand binding process.

Signaling from the epidermal growth factor (EGF) receptor is triggered by the binding of ligands such as EGF or transforming growth factor alpha (TGF-alpha) and subsequent receptor dimerization. An understanding of these processes has been hindered by the lack of structural information about the ligand-bound, dimerized EGF receptor. Using an NMR-derived structure of EGF and a homology model of the major ligand binding domain of the EGF receptor and experimental data, we modeled the binding of EGF to this EGF receptor fragment. In this low resolution model of the complex, EGF sits across the second face of the EGF receptor L2 domain and EGF residues 10-16, 36-37, 40-47 bind to this face. The structural model is largely consistent with previously published NMR data describing the residues of TGF-alpha which interact strongly with the EGF receptor. Other EGF residues implicated in receptor binding are accounted by our proposal that the ligand binding is a two-step process with the EGF binding to at least one other site of the receptor. This three-dimensional model is expected to be useful in the design of ligand-based antagonists of the receptor.

Algorithms↗
PubMed1994

Effect of intracellular pH and two growth factors, epidermal growth factor and human hepatocyte growth factor, on DNA synthesis in non-regenerating and regenerating hepatocytes and hepatoma cells.

I examined the effects of intracellular pH (pHi) and the growth factors, epidermal growth factor (EGF) and human hepatocyte growth factor (HGF), on DNA synthesis in non-regenerating hepatocytes, regenerating hepatocytes and hepatoma cells. Non-regenerating and regenerating hepatocytes were isolated from the livers of intact adult rat and of the adult rat 24 hours after 70% hepatectomy, respectively. Hep G2 cells, a human hepatoma cell line, was employed as hepatoma cells. Regenerating hepatocytes and Hep G2 cells, but not non-regenerating hepatocytes displayed increased DNA synthesis with increasing pHi in the absence of EGF and HGF. However, non-regenerating hepatocytes displayed little increase, regenerating hepatocytes displayed substantial increase in DNA synthesis with increasing pHi in the presence of EGF or HGF. In contrast, Hep G2 cells displayed decreased DNA synthesis in the presence of HGF but not EGF. These findings indicate that pHi influences the fashion of proliferation in hepatocytes and cancer cells. EGF and HGF stimulate DNA synthesis in hepatocyte and inhibit that in cancer cell, suggesting that increasing pHi and administration of these growth factors may be one of the effective treatment for hepatoma.

Animals↗
PubMed1995

Androgenic and antiandrogenic control on epidermal growth factor, epidermal growth factor receptor, and androgen receptor expression in human prostate cancer cell line LNCaP.

Both androgen and antiandrogen treatments enhance the proliferation rate of the hormone-dependent prostate cancer cell line LNCaP, expressing a mutated androgen receptor (AR). We studied the modification of the expression of epidermal growth factor (EGF), of its receptor (EGF-R), and of androgen receptor (AR) in the LNCaP cell line, under basal conditions and during androgen (R1881) and antiandrogen hydroxy-flutamide (OH-FLU) treatment. After prolonged R1881 administration, a marked increase of EGF release was observed, completely blocked by the addition of OH-FLU. The Scatchard plot analysis of EGF-R binding revealed two classes of binding sites with high and low affinity. The administration of OH-FLU alone or combined with R1881 did not modify the affinity constants, while the low-affinity component disappeared after androgen administration. Both androgen and antiandrogen administration led to a significant increase of the EGF-R high-affinity component. AR mRNA and protein levels were downregulated by R1881 treatment. Following OH-FLU administration, AR mRNA was slightly downregulated, and there was not a strict parallelism between AR mRNA levels and AR binding capacity. When combined with R1881, OH-FLU partially counteracted the androgen-induced AR downregulation. Our data show that EGF-R binding capacity is the only parameter constantly raised in cell proliferation with respect to quiescent cells, and highlights the nonunivocal action of OH-FLU on androgen-induced effects.

Androgen Antagonists↗
PubMed1990

Antiinflammatory effects of polypeptide growth factors. Platelet-derived growth factor, epidermal growth factor, and fibroblast growth factor inhibit the cytokine-induced expression of the alternative complement pathway activator factor B in human fibroblasts.

The synthesis of complement components in human fibroblasts is modulated by mediators of inflammation such as cytokines. In particular, interleukin-1 (IL-1) and tumor necrosis factor (TNF) induce time- and dose-dependent increases in the synthesis of complement proteins factor B (FB), C3, and factor H (FH). Polypeptide growth factors are also soluble mediators released during inflammation and able to modulate many fibroblast functions. We have studied the effects of polypeptide growth factors platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and fibroblast growth factor (FGF) on the synthesis of complement proteins in cultured human fibroblasts. PDGF, EGF, and FGF alone did not affect the level of synthesis of any of the complement proteins analyzed, but simultaneous incubation of PDGF, EGF, or FGF with IL-1 and TNF resulted in a dose-dependent inhibition of the cytokine-enhanced expression of FB. Inhibition of FB synthesis was observed between 4 and 8 h of exposure to PDGF and persisted for 4 h after the removal of the growth factor. Analysis of steady-state levels of specific FB mRNA suggested that PDGF-induced inhibition of FB synthesis is mediated at a pretranslational level and that it requires new protein synthesis. The effect of the growth factors was limited to FB, with marginal or no inhibition on the cytokine-enhanced synthesis of C3 and FH, excluding the possibility that the inhibitory effects of PDGF, EGF, and FGF on FB synthesis were due to a negative modulation of the growth factors on cytokine cell membrane receptors. Specific inhibition of cytokine-induced increases in FB synthesis by the growth factors may represent down regulation of the acute inflammatory process, further permitting progression to processes of tissue repair and remodeling. Study of the interactions between cytokines and growth factors in the regulation of synthesis of complement proteins may also provide a system for investigating mechanisms of signal transduction of both polypeptide growth factors and cytokines.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1989

Platelet-derived growth factor, epidermal growth factor, and insulin-like growth factor I regulate specific cell-cycle parameters of human diploid fibroblasts in serum-free culture.

The growth regulation of human diploid fibroblasts by platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin-like growth factor I (IGF-I) (somatomedin C), dexamethasone, and transferrin was investigated in a serum-free, chemically defined culture system. Cell-cycle kinetic parameters were determined using 5'-bromodeoxyuridine (BrdU) incorporation and flow cytometric analysis with the DNA-specific dye Hoechst 33258. We found that PDGF and EGF regulate the proportion of cells capable of entering the cell cycle from the quiescent state, with smaller effects upon the rate of cell transition from G1 into S phase. IGF-1, on the other hand, regulates the rate of cell exit from G1 without affecting the cycling fraction. Transferrin and dexamethasone showed less effect upon the cell-cycle kinetics under these culture conditions. The data provide functional evidence that PDGF and EGF regulate similar cell-kinetic parameters in human fibroblast cultures. IGF-I is functionally distinct from both PDGF and EGF in its role of regulating G1 exit rate without affecting the cycling fraction. These observations made by BrdU-Hoechst flow cytometric techniques provide a novel perspective on the regulatory effects exerted by different classes of growth factors, and suggest a mode of interdependence of these mitogens in regulating the net growth rate which could be a feature of growth regulation in vivo. These data also provide a different perspective on the regulation of the growth of fibroblast-like cells than that of the "competence/progression" cell-cycle model.

Adult↗
PubMed1989

Differential phenotypic expression induced in cultured rat astroblasts by acidic fibroblast growth factor, epidermal growth factor, and thrombin.

We compared the effects of three growth factors, acidic fibroblast growth factor (aFGF), epidermal growth factor (EGF), and thrombin, on rat astroblast proliferation, morphology, glutamine synthetase-specific activity, and phenotypic expression of proteins. In vitro experiments were made on 20-day-old primary cultures. Astroblast proliferation was stimulated transiently (after 48 h treatment) by the three growth factors, while the cell glutamine synthetase activity began to increase significantly only after 3 days of treatment. Acidic FGF and EGF, but not thrombin, modified the cell morphology. The effects on phenotypic expression were first determined after 5 days of treatment to minimize the mitogenic effect of the factors. Proteins synthesized during the last 18 h of the treatments were separated by two-dimensional polyacrylamide gel electrophoresis. About 600 spots were compared, 54 were modulated by the various treatments, 13 were altered similarly by all three factors, 28 by aFGF and EGF, 7 by only aFGF, 3 by only EGF, and 3 by only thrombin. These results indicate a large similarity of effects between aFGF and EGF (41 proteins) and show that these factors elicit a more extended modulation of the phenotypic expression than thrombin (13 proteins). Each of the three factors has a few specific effects, which suggests that even for aFGF and EGF, which are supposed to elicit their effects through membrane receptor-associated tyrosine kinase activity, some specificity appears in their mechanism of action. A model is proposed to suggest that cell maturation is characterized by the modulation of the synthesis of many proteins which can be grouped into classes. Each class appears to be under the control of one regulatory element. The specificity of the effect of a growth factor should result from the activation of a specific combination of such regulatory elements. Analysis of the proteins after only 18 h of treatment, when neither proliferation nor maturation were significantly affected, showed that 11 proteins were regulated only at that time. These proteins could be related to intermediate steps of the growth factor signal transduction.

Animals↗
PubMed1997

Differential effects of basic fibroblast growth factor, epidermal growth factor, transforming growth factor-alpha, and insulin-like growth factor-I on a hypothalamic gonadotropin-releasing hormone neuronal cell line.

Recent studies in several neuronal lineages suggest that extrinsic factors such as polypeptide growth factors regulate various stages of neuronal development, from initial commitment of multipotent progenitors to induction of specific gene expression that is characteristic of terminal neuronal differentiation. In the present study, immortalized hypothalamic neurons of the GT1-1 lineage were used to analyze proliferative, as well as morphological and molecular differentiation actions of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and insulin-like growth factor-I (IGF-I). These effects were compared with those induced by specific activators of protein kinase A and C pathways, which potently inhibited cell proliferation and gonadotropin-releasing hormone (GnRH) gene expression, but stimulated morphological neuronal maturation as determined by the length and number of neurite outgrowth. bFGF exerted a broad spectrum of stimulatory effects, increasing the rate of proliferation measured both by the incorporation of 3H-thymidine and by cell number, and parameters of terminal differentiation, such as neurite outgrowth and induction of gene expression. bFGF stimulated the expression of the hybrid transgene-containing portions of the rat GnRH promoter. In contrast, EGF, TGF-alpha, and IGF-I inhibited cell proliferation, while having subtle effects on neurite outgrowth. Thus, GT1-1 cells appear to be differentially responsive to distinct neurotrophic factors, providing a model for studying the specific effects of neurotrophic factors on functional differentiation, migration, and connectivity of hypothalamic neurons.

Animals↗
PubMed1985

Fibroblast growth factor, epidermal growth factor and insulin exert a neuronal-like influence on acetylcholine receptors in aneurally cultured human muscle.

Fibroblast growth factor (FGF), epidermal growth factor (EGF) and insulin added in combination to the culture medium in which normal human muscle was cultured caused a 4.0-fold (P less than 0.005) increase of the total number of nicotinic acetylcholine receptors (AChRs) and a 4.5-fold (P less than 0.001) increase in AChR aggregation. Individually, only FGF caused a 3.0-fold increase (P less than 0.005) in AChR aggregation, without influencing the total number of AChRs. To the contrary, insulin alone caused a 2.0-fold increase (P less than 0.05) in the total number of AChRs without influencing AChR aggregation. These findings show that these three polypeptide growth factors exert a neuronal-like influence on cultured human muscle in regard to AChRs.

Culture Techniques↗
PubMed1991

Effects of pretreatment with basic fibroblast growth factor, epidermal growth factor and nerve growth factor on neuron survival and neovascularization of superior cervical ganglion transplanted into the third ventricle in rats.

Effects of short-term treatment with basic fibroblast growth factor (FGF), epidermal growth factor (EGF) and nerve growth factor (NGF) on neurite outgrowth of superior cervical ganglia (SCG) in culture or on neuron survival and neovascularization of SCG in a transplantation system were examined in rats. SCG were preincubated with FGF, EGF and/or NGF for 30 min and cultured with drug-free medium for 2 days. FGF or EGF neither promoted neurite outgrowth of SCG nor potentiated the NGF-induced neurite elongation in culture. In the transplantation study, SCG were exposed to these factors for 30 min and grafted into the third ventricle of adult rats for 14 days. Although pretreatment of NGF, FGF, EGF or the combination of NGF and EGF were not effective, there was better neuron survival in SCG grafts pretreated with 1 micrograms/ml NGF and 1 micrograms/ml FGF together. In addition, density of capillaries in these grafts was significantly greater than in the other group tested. These results suggest that the synergistic interaction between NGF and FGF cause rapid neovascularization, which can prevent neuron death after transplantation.

Analysis of Variance↗
PubMed1991

BALB/c-3T3 fibroblasts resistant to growth inhibition by beta interferon exhibit aberrant platelet-derived growth factor, epidermal growth factor, and fibroblast growth factor signal transduction.

Several lines of evidence now exist to suggest an interaction between the platelet-derived growth factor (PDGF) growth-stimulatory signal transduction pathway and the beta interferon (IFN-beta) growth-inhibitory signal transduction pathway. The most direct examples are inhibition of PDGF-mediated gene induction and mitogenesis by IFN-beta and the effects of activators and inhibitors of the IFN-inducible double-stranded RNA-dependent eIF2 kinase on expression of PDGF-inducible genes. To further investigate the nature of this PDGF/IFN-beta interaction, we selected BALB/c-3T3 cells for resistance to growth inhibition by IFN-beta and analyzed the phenotypes of resulting clonal lines (called IRB cells) with respect to PDGF signal transduction. Although selected only for IFN resistance, the IRB cells were found to be defective for induction of growth-related genes c-fos, c-myc and JE in response to PDGF. This block to signal transduction was not due to loss or inactivation of PDGF receptors, as immunoprecipitation of PDGF receptors with antiphosphotyrosine antibodies showed them to be present at equal levels in the BALB/c-3T3 and IRB cells and to be autophosphorylated normally in response to PDGF. Furthermore, treatment with other peptide growth factors (PDGF-AA, fibroblast growth factor, and epidermal growth factor) also failed to induce c-fos, c-myc, or JE expression in IRB cells. All of these growth factors, however, were able to induce another early growth-related gene, Egr-1. The block to signaling was not due to a defect in inositol phosphate metabolism, as PDGF treatment induced normal calcium mobilization and phosphotidylinositol-3-kinase activation in these cells. Activation of protein kinase C by phorbol esters did induce c-fos, c-myc, and JE in IRB cells, indicating that signalling pathways distal to this enzyme remained intact. We have previously shown that IFN-inducible enzyme activities, including double-stranded RNA-dependent eIF2 kinase and 2',5'-oligoadenylate synthetase, are normal in IRB cells. The finding that the induction of multiple growth-related genes by several independent growth factors is inhibited in these IFN-resistant cells suggests that there is a second messenger common to both growth factor and IFN signaling pathways and that this messenger is defective in these cells.

Animals↗
PubMed1984

Comparison of rapid changes in surface morphology and coated pit formation of PC12 cells in response to nerve growth factor, epidermal growth factor, and dibutyryl cyclic AMP.

Scanning and transmission electron microscopic studies were carried out on the rapid cell surface response of PC12 pheochromocytoma cells to treatment with nerve growth factor (NGF), epidermal growth factor (EGF), and dibutyryl cyclic AMP. EGF induced a rapidly initiated series of surface changes identical to those previously observed with NGF. Ruffles appear over the dorsal surface of the cells by 30 s, are prominent at 3 min, and are absent by 7 min. Microvilli disappear as dorsal ruffles become prominent. Peripheral ruffles are seen by 3 min, are prominent on most of the cells by 7 min, and are virtually absent by 15 min. Large blebs are present on 50% of the cells by 2 h and are markedly decreased by 4 h. Within 30 s after NGF or EGF addition, an increase in the density of 60-130-nm coated pits per unit membrane is detectable. This reaches a maximum of two- to threefold in from 1 to 3 min and gradually decreases. Combined treatment with NGF and EGF increases surface ruffling and, after an early peak in coated pits which at 3 min is similar in magnitude to that observed for the separately administered factors, maintains a greater number of pits per unit area than either treatment alone. 3-d pretreatment with NGF greatly reduces the response of the cells to EGF both with respect to surface ruffling and coated pit formation while 4-h NGF pretreatment has no effect on the EGF response. Dibutyryl cyclic AMP induced none of the rapidly onsetting changes caused by NGF or EGF, and therefore it seems unlikely that cyclic AMP mediates these surface changes. Changes in cell surface architecture induced by NGF and EGF on PC12 cells and by NGF in normal sympathetic neurons (as previously described) indicates that such responses may be a widespread phenomenon associated with the interaction of at least some peptide growth factors/hormones with their receptors. These responses may represent or reflect primary events in the mechanism by which these factors act.

Adrenal Gland Neoplasms↗
PubMed1996

Effect of prostatic growth factor, basic fibroblast growth factor, epidermal growth factor, and steroids on the proliferation of human fetal prostatic fibroblasts.

To study the relationship between androgen metabolism and the pathogenesis of benign prostatic hypertrophy, we purified a growth factor from benign hyperplastic tissue of human prostates and assayed the proliferative responses of human fetal prostatic fibroblasts to the purified growth factor (hPGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), dihydrotestosterone (DHT), and estradiol (E2). Prostatic tissue extracts were fractionated using heparin-Sepharose chromatography. The fraction that eluted with 1.3-1.7 M NaCl contained the majority of mitogenic activity. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS/PAGE) of the lyophilyzed active fraction showed a band at 17,000 daltons. Human prostatic fibroblasts were isolated from fetal prostate and tested for their proliferative responses to hPGF, bFGF, EGF, DHT, and E2. hPGF, as well as bFGF and EGF, did increase tritiated thymidine incorporation into the cultured fibroblasts. DHT(10(-7) M) had a significant stimulatory effect on cell growth in serum-free media after 6 days of culture. E2(10-7 M) had no effect on cell proliferation. The combination of DHT and E2 showed no synergistic effect. We conclude that our purified hPGF, bFGF, and EGF promote cell growth directly, DHT indirectly, while E2 does not. The effect of DHT appears to be mediated via the increased production and/or secretion of growth factor(s). Possibly, the bFGF-like hPGF purified from human benign hyperplastic prostatic tissue is such a mediator.

Analysis of Variance↗