Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Autocrine”

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 883 records · Page 49Linked to original sources
PubMed1997

Interleukin-6 as a paracrine and autocrine growth factor in human prostatic carcinoma cells in vitro.

Interleukin (IL)-6 plays a significant role in genitourinary carcinomas. The present study was conducted to define the role of IL-6 in the growth of prostatic carcinoma and benign prostatic hyperplasia (BPH). An in vitro experiment was carried out using human prostatic carcinoma cell lines (LNCaP, which is androgen sensitive and slow growing, and DU145 and PC3, which are androgen insensitive and fast growing), and primary human epithelial and stromal cells derived from BPH. Cells were treated with recombinant human IL-6 or conditioned medium (CM) derived from the above cultured cells to identify possible paracrine and autocrine pathways. LNCaP was clearly responsive to exogenous IL-6 and to the CM derived from stromal cells, but not to the CM from LNCaP cells (P < 0.001). DU145 and PC3 were slightly stimulated to grow by exogenous IL-6 and the CM derived from both stromal and respective homologous cells (P < 0.01). In contrast, BPH-derived epithelial cells showed little or no response to IL-6. The stimulatory effect of CM on prostatic carcinoma cells was significantly reduced by the addition of anti-IL-6 antibody to the culture medium. Furthermore, the growth of DU145 and PC3 in serum-free medium was also inhibited by anti-IL-6 antibody (P < 0.001). All cell lines tested, except for LNCaP, secreted IL-6 into the culture medium. Results of reverse transcriptase-PCR analysis indicated that IL-6 receptor mRNA was present in all carcinoma cell lines but not in epithelial cells or stromal cells derived from BPH. These results suggest that IL-6 functions as a paracrine growth factor for LNCaP and as an autocrine growth factor for DU145 and PC3, but it has no stimulatory effect on epithelial cells derived from BPH.

Antibodies, Anti-Idiotypic↗
PubMed1995

Transforming growth factor beta 1 (TGF beta 1) is an autocrine positive regulator of colon carcinoma U9 cells in vivo as shown by transfection of a TGF beta 1 antisense expression plasmid.

A transforming growth factor beta1 (TGF beta1) antisense expression plasmid under constitutive control of the Rous sarcoma virus promoter was introduced into the highly tumorigenic and invasive colon carcinoma U9A cell line, which uses its autocrine TGF beta1 as a growth-stimulating factor. Stable transfectants were infrequent, and only the K6 transfectant exhibited 39 and 33%, respectively, of the levels of TGF beta1 mRNA and active, secreted TGF beta1 protein of the parental line. K6 exhibited no change in TGF beta2 expression, and TGF beta3 expression was not detected in either parental or transfectant cells. Compared to the parental line, the K6 antisense transfectant exhibited a 3-fold increase in lag time in anchorage-dependent colony formation. The parental line was 44 times as invasive through a collagen l-coated polycarbonate membrane in vitro as K6 cells and, after s.c. injection at low-cell inocula, U9A cells induced tumors 75 times as large in vivo as did the K6 antisense transfectant. The decreases in in vitro invasion and anchorage-dependent colony formation seen in K6 cells were largely reversed by the addition of TGF beta1. Tumors that did arise from the K6 antisense transfectant cells had lost antisense TGF beta1 expression and expressed the same TGF beta1 mRNA levels as controls. U9A cells were more metastatic to the liver after intrasplenic injection than K6 cells. These findings demonstrate a role for autocrine TGE beta1 in colon cancer tumorigenicity and invasion. They also show that a relatively small decrease in TGF beta1 levels was enough to markedly decrease colon carcinoma cell aggressiveness. This is not unprecedented, as we had found in an earlier study that a small, 2-4-fold increase in TGF beta1 protein levels in human colon cancers correlated with disease progression to metastases (E. Friedman et al., Cancer Epidemiol, Biomarkers & Prev., 4:549-554, 1995).

Animals↗
PubMed1997

Retinoic acid abolishes the calcitonin gene-related peptide autocrine system in F9 teratocarcinoma cells.

Calcitonin gene-related peptide (CGRP), expressed predominantly in F9 embryonal carcinoma cells, is both a potent chemotactic agent and an autocrine growth factor for these cells. We analyzed the effect of retinoic acid (RA)-induced differentiation of F9 cells into primitive parietal endoderm-like cells, on CGRP production and the CGRP responsiveness of these cells. Poly(A) RNA extracted from F9 cells and analysed by Northern blotting and hybridization with a CGRP probe showed a specific band of about 1200 bases corresponding to mature CGRP mRNA. This band was not detected in F9 cells treated for 6 days with RA (differentiated primitive parietal endoderm-like cells) or in PYS cells (established parietal endoderm-like cell line). During RA-induced differentiation of F9 cells, CGRP mRNA levels fell within 24 h after treatment and were almost undetectable after 2 days. RA treatment also reduced CGRP secretion by F9 cells; the effect was maximal at 3 days and remained stable thereafter. Similarly, RA rapidly reduced adenylate cyclase responsiveness to chicken CGRP (cCGRP) and human CGRP (hCGRP). An 80% fall in cAMP release into the culture medium in the presence of CGRP was observed after 24 h of RA treatment. These results demonstrate that RA rapidly abolishes the CGRP autocrine system involved in the proliferation of F9 cells, at the same time inducing their differentiation into primitive parietal endoderm. They point to the interaction between retinoic acid and growth factors in the regulation of cell proliferation and differentiation.

Adenylyl Cyclases↗
PubMedDate not supplied

The epidermal growth factor receptor is involved in autocrine growth of human bladder carcinoma cell lines.

We have previously shown that human bladder tumor cell lines may be adapted to grow in the complete absence of serum or any other growth supplement and that this can be explained on the basis of autocrine stimulation. In the present study we have extended the number of cell lines that could be established as serum-free cultures and found this capacity to be correlated with tumor malignancy. We also used the receptor blocking monoclonal antibody, mAb 528, to study its effect on tumor cell growth. Inhibition was observed in all of seven bladder carcinoma cell lines tested. A similar effect was observed in two colon carcinoma cell lines but not in a melanoma line. The results show that the EGFR is involved in autocrine growth stimulation and that the acquirement of autonomous growth capacity is likely to be an important factor in the oncogenesis of bladder tumors.

Antibodies, Monoclonal↗
PubMed1997

Proliferation of LAMA-84 and LAMA-87 cell lines is modulated by autocrine loops involving M-CSF and TGF-beta.

The erythromegakaryocytic cell line (LAMA-84) and the erythroeosinophilic cell line (LAMA-87) were used to study receptor expression and receptor-mediated response to monocyte/macrophage colony-stimulating factor (M-CSF) and transforming growth factor beta (TGF-beta), two modulators of cell proliferation. As demonstrated by Northern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR), c-fms and M-CSF mRNA were expressed in both cell lines. M-CSF was detected in the supernatant of both cell lines and addition of a neutralizing anti-M-CSF antibody inhibited cell growth. The two LAMA cell lines were found to express TGF-beta1, -beta2, and -beta3 mRNAs and to secrete TGF-beta mostly in latent form. Addition of anti-TGF-beta antibodies to the culture medium increased their proliferation, whereas TGF-beta1 inhibited cell proliferation by downregulating the c-myc mRNA. These results show that the proliferation of both LAMA cell lines is positively and negatively regulated by autocrine mechanisms, implying the presence of M-CSF and TGF-beta, respectively. They suggest that similar autocrine loops could be involved in the growth regulation of leukemic cells in vivo.

Animals↗
PubMed1997

Abnormal activation of cytokine gene expression by intracisternal type A particle transposition: effects of mutations that result in autocrine growth stimulation and malignant transformation.

This review will focus on understanding the mechanisms resulting in the deregulated expression of cytokine genes that can lead to autocrine transformation. The murine genome contains over 2000 copies of intracisternal type A particles (IAPs), which under certain circumstances can transpose to different positions in the genome. When these transpositions affect the expression of a gene that can either positively or negatively regulate cell growth, a malignant or transformed cell may arise that has different growth characteristics than the parental cells. If this mutation confers a growth advantage to the cell, a tumor may develop. IAP transpositions have been frequently observed in hematopoietic cells, and they often affect cytokine gene expression. Genetic elements that possess similar transposable characteristics are also contained in the human genome. This review will discuss how IAP transpositions can result in the autocrine transformation of hematopoietic cells.

Animals↗
PubMed1997

IL-15 functions as a potent autocrine regulator of macrophage proinflammatory cytokine production: evidence for differential receptor subunit utilization associated with stimulation or inhibition.

The cytokine IL-15 appears to mimic the stimulatory activity of IL-2 on lymphocytes by utilizing part of the IL-2R complex. Although effects of IL-15 on Mphi activities have not previously been reported, its derivation from activated Mphi suggested a possible autocrine role in regulating Mphi functions and prompted us to determine whether IL-15 modulated LPS-activated Mphi cytokine production. Whereas high IL-15 concentrations enhanced proinflammatory (i.e., TNF-alpha, IL-1, and IL-6) and anti-inflammatory (i.e., IL-10) cytokine production by two- to sixfold, extremely low IL-15 concentrations (picomolar to attomolar range) markedly and selectively suppressed Mphi proinflammatory, but not anti-inflammatory, cytokine production by two- to fourfold. The stimulation (but not the suppression) of TNF-alpha production by IL-15 required the (IL-2/IL-15) receptor beta chain, as demonstrated by receptor subunit-blocking studies and lack of stimulation of Mphi from IL-2Rbeta-deficient mice. Conversely, suppression most likely involved the alpha receptor (IL-15R alpha) because this high affinity receptor would be engaged by low concentrations of IL-15, and its inducible expression correlated with the degree of suppression in both a time- and LPS dose-dependent fashion. Moreover, Ab-mediated neutralization studies revealed that endogenous IL-15 activity regulated Mphi activation with kinetics similar to that seen in response to exogenously added IL-15: suppressor activity increased over time in correlation with IL-15R alpha gene expression. This study demonstrates a novel dose-dependent and autocrine activity of IL-15 in Mphi regulation.

Animals↗
PubMed1997

Cell scattering and migration induced by autocrine transforming growth factor alpha in human glioma cells in vitro.

In the present investigation, we have transfected a human malignant glioma cell line, U-1242 MG, and derived clones that produce transforming growth factor alpha (TGF-alpha) in an inducible manner using the tetracycline suppressible vector system. TGF-alpha expression was confirmed by Northern analysis, by ELISA, and by immunoprecipitation of metabolically labeled cells. The functional activity of the induced protein was proven by the finding of epidermal growth factor receptor (EGFR) tyrosine phosphorylation on induction of TGF-alpha. A clear effect on cell motility, i.e., cell scattering and an increased phagokinetic track area of individual glioma cells, was demonstrated. The fact that the EGFR tyrosine kinase activation was independent of cell density suggests that autocrine activation of the EGFR kinase occurred at the single-cell level. These findings are of interest, because increased cell motility is most likely a requirement for glioma cell invasion in vivo. The results imply that as a result of coexpression of EGFR and its ligand, individual glioma cells are capable of acting as independent autocrine locomotory units.

Antibodies, Monoclonal↗
PubMed1998

IL-10 as an autocrine regulator of CSF secretion by monocytes: disparate effects on GM-CSF and G-CSF secretion.

In previous studies of endogenous granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) production, we found several differences in the secretion pattern within and between different cell systems; for example, CSF secretion by endothelial cells is not affected by any major downregulatory factors, whereas monocyte CSF secretion is modulated by several mechanisms. In this study, we characterized the factors that inhibit CSF secretion by monocytes. Three cytokines have inhibitory effects: interleukin (IL)-4, IL-10, and IL-13. Among these, IL-4 and IL-10 have higher potency than IL-13. IL-4 and IL-13 affect GM-CSF and G-CSF secretion to the same extent. In contrast, exogenously added IL-10 has a stronger inhibitory effect on GM-CSF secretion than on G-CSF secretion. We also found that monocytes produce IL-10 with an autocrine downregulatory effect, and that this autocrine IL-10 reaches concentrations at which in most cases only GM-CSF (not G-CSF) secretion is significantly affected. We postulate that the disparate effect of IL-10 on monocyte secretion of the two CSFs reflects their physiological functions, with GM-CSF being mainly a proinflammatory cytokine working in the local compartment and G-CSF functioning mainly as a cell recruiting factor.

Granulocyte Colony-Stimulating Factor↗
PubMed1998

Autocrine and paracrine apoptosis are mediated by differential regulation of Fas ligand activity in two distinct Jurkat T cell populations.

Fas ligand (FasL) produced by activated T cells mediates autocrine-induced apoptosis to limit T cell expansion. To investigate the regulation of FasL activity, Jurkat cells were stably transfected with a 2.3-kb fragment of human FasL promoter that controlled the expression of a GFP reporter gene. Two populations of Jurkat cells with different levels of GFP expression were obtained. One population constitutively expressed high levels of GFP (GFP+), while the other population expressed low levels of GFP (GFP-). The level of GFP expression in the two populations correlated with their levels of FasL transcription and its functional activity. Autocrine regulation of apoptosis was demonstrated by increased FasL activity after stimulation of GFP- cells with anti-CD3, phorbyl myristyl acetate plus ionomycin, or Con A. Paracrine regulation of apoptosis was suggested by the induction of apoptosis of GFP- cells after coculture with unstimulated GFP+ cells. GFP+ cells exhibited a decreased sensitivity to FasL-mediated apoptosis compared with GFP- cells. Furthermore, the cell surface expression of Fas and CD4 was lower on GFP+ cells than GFP- cells, whereas the expression of CD45RO was higher. A decreased level of IL-2 was produced by GFP+ cells after phorbyl myristyl acetate and ionomycin stimulation. Our results indicate that a subpopulation of T cells that express low levels of FasL and IL-2, which are responsive to up-regulation of these molecules after activation, can undergo apoptosis either by suicide after activation or by a paracrine pathway mediated by T cells that constitutively express higher levels of FasL.

Apoptosis↗
PubMed1997

8-Chloro-cyclic AMP inhibits autocrine and angiogenic growth factor production in human colorectal and breast cancer.

8-Chloro-cyclic AMP (8-Cl-cAMP) is a cAMP analogue that specifically down-regulates type I protein kinase A, a signaling protein directly involved in cell proliferation and neoplastic transformation, and that causes growth inhibition in a variety of human cancer cell types. In this report, we have investigated the effects of 8-Cl-cAMP on the expression of several growth factors in human colon (GEO and LS174T) and breast (MDA-MB468) cancer cell lines. 8-Cl-cAMP treatment caused in the three cancer cell lines a significant dose- and time-dependent inhibition in the expression of various endogenous autocrine growth factors, such as transforming growth factor alpha, amphiregulin, and CRIPTO, and of two angiogenic factors, such as vascular endothelial growth factor and basic fibroblast growth factor, at both the mRNA and protein levels. Furthermore, 8-Cl-cAMP treatment markedly inhibited the ability of all three cell lines to invade a basement membrane matrix in a chemoinvasion assay. Finally, 8-Cl-cAMP-induced inhibition of GEO tumor growth in nude mice was accompanied by a significant suppression of transforming growth factor alpha, amphiregulin, CRIPTO, basic fibroblast growth factor, and vascular endothelial growth factor production by the tumor cells, and of neoangiogenesis, as detected by factor VIII staining of host blood cells. These results demonstrate that 8-Cl-cAMP is a novel anticancer drug that inhibits the production of various autocrine and paracrine tumor growth factors that are important in sustaining autonomous local growth and facilitate invasion and metastasis.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

Differential responsiveness to autocrine and exogenous transforming growth factor (TGF) beta1 in cells with nonfunctional TGF-beta receptor type III.

The two major intestinal epithelial cell lineages are columnar fluid-absorbing cells and mucin-producing goblet cells. High levels of transforming growth factor (TGF) beta1 are found surrounding postmitotic cells in the colonic crypt, suggesting that TGF-beta1 mediates the maturation and growth inhibition of both epithelial cell types. However, we now show that the injection of recombinant TGF-beta1 into mice leads to an enrichment of goblet cells, indicating that these normal epithelial cells are resistant to TGF-beta1. In support of this interpretation, each of two independently isolated cell lines modeling normal colon goblet cells was also growth resistant to exogenous TGF-beta1 but made levels of TGF-beta receptor (TbetaR) I, TbetaRII, and TbetaIII mRNA and protein equal to those made by two TGF-beta1-sensitive cell lines. No mutations were found in the alk5 or alk2 forms of TbetaRI or in TbetaRII; these receptors were found on the cell surface, although they could not bind 125I-labeled TGF-beta1. TbetaRIII binds TGF-beta1, concentrates it, and presents it to TbetaRII. The major TbetaRIII form, betaglycan, did not undergo normal posttranslational modification in either of the goblet cell lines and could not bind 125I-labeled TGF-beta1; thus, it was nonfunctional. TGF-beta resistance was overcome by raising TGF-beta1 levels 100-fold, at which point TbetaRII could bind TGF-beta1. Signaling initiated by these higher TGF-beta1 levels was blocked by the expression of dominant negative TbetaRII, demonstrating that TbetaRII and TbetaRI were functional. Cells resistant to exogenous TGF-beta1 maintained functional cell surface TbetaRI and TbetaRII to mediate responses to autocrine TGF-beta1, which controlled the maturation of the adhesion protein integrin beta1. Expression of dominant negative TbetaRII in goblet cells greatly inhibited the conversion of the beta1 integrin from its precursor to its mature form. Thus, in normal intestinal epithelial goblet cells, TbetaRI and TbetaRII can respond to autocrine but not exogenous TGF-beta without the participation of TbetaRIII. Absorptive epithelial cells are growth inhibited by TGF-beta1 both in vivo and in vitro; therefore, the loss of functional TbetaRIIIs on goblet cells allows differential regulation of the two major intestinal epithelial cell types.

Activin Receptors, Type I↗
PubMed2004

Keratinocyte growth factor and autocrine repair in airway epithelium.

BACKGROUND: Delayed or nonreepithelialization of the large conducting airway (ie, trachea and bronchus) is a clinically recognized but poorly understood result of airway trauma. This delay results in granulation tissue formation and scarring, which impairs mucocilliary transport and can critically compromise gas exchange. Keratinocyte growth factor (KGF) is a known epithelial cell mitogen that is derived from mesenchymal cells. We previously observed its expression in injured tracheal explants, and in the present study we investigated its origin. DESIGN: Freshly isolated porcine tracheal epithelial cells were cytospun onto glass slides for immunohistochemical identification and localization of KGF and for in situ hybridization localization of its messenger RNA. Polymerase chain reaction analysis for KGF was also performed. RESULTS: Freshly isolated respiratory epithelial cells were identified as being of epithelial origin and uncontaminated by fibroblasts, as evidenced by stains that were positive for AE3 and negative for vimentin. Immunohistochemical analysis and in situ hybridization revealed a subset of cells that were positive for both the protein and the message for KGF. CONCLUSION: This subset of KGF-expressing respiratory epithelial cells may participate in a hitherto undescribed autocrine loop for stimulating KGF production in response to injury.

Animals↗
PubMed2000

HGF is an autocrine growth factor for skeletal muscle satellite cells in vitro.

Muscle satellite cell activation following injury is essential for muscle repair, and hepatocyte growth factor/scatter factor (HGF) was the first growth factor shown to be able to stimulate activation and early division of adult satellite cells in culture and in muscle tissue. In addition, HGF was shown to be present in uninjured and injured skeletal muscle. Experiments in this report demonstrate that cultured satellite cells also synthesize and secrete HGF. Reverse transcription-polymerase chain reaction (RT-PCR) was used to demonstrate the presence of HGF mRNA in cultured adult satellite cells as early as 12 h from the time of plating. Message content was detectable at early times in culture and appeared to increase between 36 and 48 h. HGF protein expression was demonstrated during this time period by immunofluorescence localization; HGF was localized to mononucleated cells and multinucleated myotubes. HGF message was not detectable in muscle-derived fibroblast clones, and fibroblast-like cells in satellite cell cultures were negative for HGF by immunofluorescence analysis. Furthermore, Western blot analysis revealed the presence of HGF in satellite cell culture conditioned medium, associated with the cell surface and inside cells. Finally, the addition of neutralizing HGF antibodies during the proliferation phase in culture (42-90 h) significantly reduced cell proliferation. These experiments indicate that HGF is expressed by cultured satellite cells and that endogenous HGF from satellite cells can act in an autocrine fashion. Because HGF plays a central role in satellite cell activation, it is likely that direct administration of HGF into damaged muscle may represent a potentially useful approach for stimulating muscle repair. This approach may also be useful in enhancing the efficiency of myoblast transplantation in vivo.

Animals↗
PubMed1999

Transforming growth factor-beta1 is an autocrine mediator of U937 cell growth arrest and differentiation induced by vitamin D3 and retinoids.

Vitamin D and retinoids cooperate to inhibit the proliferation and induce the differentiation of human myelomonocytic U937 leukemia cells. In the present work, we investigated the role of TGF-beta as an endogenous mediator of this process. We found that the TGF-beta1 precursor began to accumulate in cell culture supernatants soon after the addition of 1alpha,25 dihydroxyvitamin D3 (VD) and retinoids. We used neutralizing antibodies (AbTGF-beta) and antisense oligonucleotide (AS Oligo) to inhibit its possible effects. Our data demonstrated that AbTGF-beta partially inhibit the expression of the differentiated phenotype, as assessed by measurement of phagocytic activity, response to the chemotactic peptide fMLP, and lysozyme secretion. AS Oligo was also inhibitory, and the effects of AS Oligo and AbTGF-beta were cumulative. Cell growth inhibition induced by VD and retinoids was completely reversed, and differentiation was reduced by about 75% when both inhibitors were associated. Time course experiments based on the delayed addition of AbTGF-beta and AS Oligo showed that TGF-beta1 was required for cell differentiation 24 h after the addition of inducers. Studies on TGF-beta receptors revealed that, while the expression of type II receptor was stable, the level of type I TGF-beta receptor mRNA and the expression of the protein began to decline early during the differentiation process. As a whole, these results support the notion that an autocrine TGF-beta pathway, activated by VD and retinoids in U937 cells, is involved in the early steps of the process leading to cell growth arrest and differentiation.

Antibodies↗
PubMed1994

Expression of autocrine motility factor receptor in colorectal cancer as a predictor for disease recurrence.

BACKGROUND: New biologic prognostic factors are needed to guide the treatment of patients with colorectal cancer. The prognostic value of the altered expression of the cell surface glycoprotein gp78, which has been implicated in tumor-cell invasion and metastasis as an autocrine motility factor (AMF) receptor, was evaluated. METHODS: The level of expression of AMF receptor gp78 was analyzed immunohistochemically in tumor specimens from 118 patients who had undergone surgery for colorectal cancer. Multivariate analysis was used to determine whether gp78 expression status was correlated with patient prognosis. RESULTS: Among the 118 patients studied, the 5-year survival rate for the 51 patients who had gp78-positive tumors was significantly poorer that that of the 67 patients who had gp78-negative tumors (49.8% vs. 89%). The incidence of gp78 positivity was correlated with tumor progression as reflected by histologic type, depth of invasion, lymph node metastasis, vessel invasion, and tumor stage. Among the 101 patients who underwent curative resection, the difference in disease free survival between patients with gp78-positive tumors and those with gp78-negative tumors was significant. This significant difference remained among patients who had Stage II tumors. Multivariate analysis with the Cox regression model indicated that gp78 positivity was a good predictor of disease recurrence, ranking with extent of tumor invasion (T classification) and lymph node status (N classification). CONCLUSIONS: Increased expression of gp78 is correlated with a high incidence of recurrence and, consequently, with decreased survival of patients with colorectal cancer. Expression of gp78 might be of prognostic value in these patients.

Adult↗
PubMed2001

Significance of autocrine motility factor receptor gene expression as a prognostic factor in non-small-cell lung cancer.

Autocrine motility factor receptor (AMF-R) has been shown to play an important role in tumor cell migration, invasion and metastasis. We have detected AMF-R expression in tissue specimens from patients with non-small-cell lung cancer (NSCLC) and have assessed their clinical characteristics. Using RT-PCR and immunohistochemistry, we quantified the expression of AMF-R in 47 patients with NSCLC who underwent curative tumor resection, to investigate the relationship between AMF-R expression and clinicopathologic factors and prognosis. RT-PCR results agreed well with the immunohistochemic results (p < 0.0001). In 47 NSCLC patients, 34 (72.3%) samples were evaluated as having high AMF-R gene expression. AMF-R gene expression was significantly associated with lymph node metastasis and stage (p = 0.0295 for lymph node metastasis, p = 0.0152 for stage). The overall survival rate for patients with high AMF-R gene-expressing tumors was significantly worse than for those whose tumors had low AMF-R expression (p = 0.0029). Multivariate analysis also showed that AMF-R gene expression was significantly related to survival (p = 0.0165). These data indicate that AMF-R may contribute to tumor progression and that AMF-R gene expression can serve as a useful prognostic marker in NSCLC.

Adenocarcinoma↗
PubMed2000

Transforming growth factor-beta is an autocrine mitogen for a novel androgen-responsive murine prostatic smooth muscle cell line, PSMC1.

A prostatic smooth muscle cell line (PSMC1) was established from the dorsolateral prostate of p53 null mice. The cell line is nontumorigenic when inoculated subcutaneously, under the renal capsule or intraprostatically in syngeneic mice. These cells express alpha-smooth muscle actin (alpha-SMA), indicating their smooth muscle origin, and TGF-beta significantly enhances expression of alpha-SMA. The cells express both androgen receptor (AR) mRNA and protein, and respond mitogenically to physiological concentrations of androgens. PSMC1 cells produce significant amounts of TGF-beta, which stimulates growth by an autocrine mechanism. Dihydrotestosterone (DHT) increases proliferation of PSMC1 cells by promoting TGF-beta secretion. Considering the significant inhibitory effect of TGF-beta on prostatic epithelial cells and its stimulatory effect on the PSMC1 cells, we postulate that TGF-beta produced by prostatic smooth muscle cells may have a paracrine effect on the prostatic epithelium. We also postulate that TGF-beta may be involved in the etiology of benign prostatic hyperplasia (BPH) by stimulating excessive stromal proliferation. Line PSMC1 is the first reported androgen-responsive murine smooth muscle cell line. It will be useful for in vivo and in vitro experiments to study the mechanisms of androgen action on prostatic stroma and for delineating the interactions that occur between prostatic smooth muscle and epithelium that may lead to prostatic diseases such as BPH.

Androgens↗