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At least 613 records · Page 34Linked to original sources
PubMed2005

Autocrine activation of DNA synthesis in prothoracic gland cells of the silkworm, Bombyx mori.

Autocrine activation of DNA synthesis in prothoracic gland cells in last instar larvae of the silkworm, Bombyx mori, was studied using both a long-term in vitro organ culture system and immunocytochemical labeling with 5-bromo-2'-deoxyuridine (BrdU). When prothoracic glands were incubated in a small volume of culture medium (10 microl/gland), the numbers of DNA-synthesizing cells per gland increased significantly, and DNA synthesis was stimulated less by hemolymph, as compared with glands incubated in a large volume (50 microl/gland). Moreover, glands cultured in groups (6 glands per group in a 50-microl drop) also resulted in much higher levels of DNA synthesis than those cultured individually in a 50-microl drop. The mechanism by which alternation of the volume of the incubation medium results in changes in the levels of DNA synthesis was further examined. When prothoracic glands were incubated in medium (50-microl drop per gland) that was preconditioned with glands (in a 10-microl drop individually), a dramatic increase in DNA synthesis activity was also observed, indicating that prothoracic glands may release a factor that stimulates their own DNA synthesis. The growth-promoting factor was further characterized and it was found that the factor is heat stable, and its molecular weight was estimated to be between 1,000 and 3,000 Da. Moreover, the factor also stimulated corpus allatum cell DNA synthesis in vitro. Injection of concentrated putative growth-promoting factor into day 4 last instar-ligated larvae greatly increased cell DNA synthesis of the prothoracic glands, indicating the in vivo function of the present autocrine factor.

Animals↗
PubMed2006

Both prothoracicotropic hormone and an autocrine factor are involved in control of prothoracic gland ecdysteroidogenesis in Locusta migratoria and Schistocerca gregaria.

In Bombyx mori, ecdysteroidogenesis by the prothoracic glands (PGs) is controlled by both prothoracicotropic hormone (PTTH) and a factor secreted by the glands themselves. This factor, which is active both in vitro and in vivo, has been named 'autocrine factor' (AF). To find out whether or not this dual control also exists in other species, in particular in hemimetabolous ones, we applied similar methods as were used to discover AF in Bombyx to the locusts Locusta migratoria and Schistocerca gregaria. Our results unequivocally show that locust PGs also secrete an as yet unidentified autocrine factor. Possible roles of AF are discussed.

Animals↗
PubMed2005

Functional erythropoietin autocrine loop in melanoma.

Although erythropoietin (Epo) is a known stimulator of erythropoiesis, recent evidence suggests that its biological functions are not confined to hematopoietic cells. To elucidate the role of Epo and erythropoietin receptor (EpoR) in melanoma, we examined the expression and function of these proteins in melanocytes and melanoma cells. We found increased expression of Epo in melanoma cells compared to melanocyte in vitro. EpoR was also strongly expressed in all of the melanoma cell lines and two of the three melanocyte cell lines examined. Epo expression was significantly higher in melanoma than in benign nevi as determined by immunohistochemistry. Although melanoma cells secreted Epo in normoxic condition in vitro, hypoxia and CoCl(2) treatment increased Epo secretion. EpoR in melanoma cells was functional, because exogenous Epo increased melanoma resistance to hypoxic stress, pretreatment of melanoma cells with Epo significantly increased resistance to dacarbazine treatment, and Epo increased the phosphorylation of EpoR, RAF, and MEK. In conclusion, we demonstrated constitutive expression of Epo and EpoR as well as autonomous secretion of Epo by melanoma cells, indicating a novel autocrine loop of Epo in melanoma. The results suggest that the autocrine and paracrine functions of Epo might play a role in malignant transformation of melanocytes and in the survival of melanoma cells in hypoxia and other adverse conditions.

Blotting, Western↗
PubMed1992

Calcitonin gene-related peptide: an autocrine growth factor with regulatory activity in vitro.

We show that an autocrine system for calcitonin gene-related peptide (CGRP) exists in F9 teratocarcinoma cells. Synthesis of CGRP by F9 cells was demonstrated by measuring the peptide concentration in cells and medium and by determining specific mRNA in cells. During six days of culture, CGRP secretion did not vary significantly in the medium, while intracellular CGRP and CGRP mRNA levels increased. F9 cells contained a CGRP-sensitive adenylate cyclase system and CGRP increases the accumulation of cAMP in the culture medium. Interestingly affinity purified antibodies against CGRP specifically inhibited growth of F9 cells by 50%. CGRP therefore stimulates F9 cell growth by an autocrine process, suggesting that CGRP may be a growth factor during early embryogenesis.

Animals↗
PubMed1987

Interleukin-1 derived from human monocytic leukemia cell line JOSK-I acts as an autocrine growth factor.

Interleukin-1 (IL-1) enhances the growth of human monocytic leukemia cell line JOSK-I cells, which were recently established in our laboratory and which were demonstrated to produce a high level of IL-1 constitutively, in liquid as well as semisolid culture systems. Concomitantly, IL-1 stimulated the prostaglandin E2 synthesis and nitroblue tetrazolium dye-reducing capacity of JOSK-I cells. This indicates that IL-1 may act as autocrine growth factor for monocytes, and also suggests the possibility that this autocrine stimulation may play an important role in the pathophysiology of monocytic leukemia in vivo.

Cell Differentiation↗
PubMed1998

The autocrine derivation of the opioid growth factor, [Met5]-enkephalin, in ocular surface epithelium.

Endogenous opioid peptides serve as growth factors in developing, renewing, healing, and neoplastic cells and tissues. A native opioid peptide, [Met5]-enkephalin, termed opioid growth factor (OGF), has been discovered to regulate DNA synthesis in the epithelium of the ocular surface. OGF and its receptor zeta have been localized in both the basal and suprabasal cells of the epithelium. This study examined the hypothesis that OGF is an autocrine growth factor. Using probe for preproenkephalin (PPE) mRNA that encodes OGF, and in situ hybridization techniques, silver grains related to PPE mRNA were detected in both basal and suprabasal cells of the central and peripheral cornea, limbus, and conjunctiva. No distinct regional differences in the presence or location of message, as reflected by the density and distribution of PPE mRNA signal, were noted. These results demonstrate that a growth factor known to serve as a tonic, inhibitory, and receptor-mediated influence on the epithelium of the ocular surface is derived in an autocrine manner, thereby permitting local control of homeostatic cellular replication.

Animals↗
PubMed1998

Role of autocrine stimulation for the effects of cyclic AMP on protein and lipid phosphorylation in platelets activated by particles.

We have compared responses in platelets stimulated with the particulate materials, Intralipid (liposome-suspension) and a potential contrast medium IEEC (1'-(ethyloxycarbonyloxy)-ethyl-5-acetyl-amino-3-(N-methyl-acetyla mino)-2,4,6-triiodo-benzenecarboxylate coated with human serum albumin), with and without forskolin and inhibitors of autocrine stimulation (IAS: an ADP-removing system of creatine phosphate/creatine phosphokinase; RGDS to prevent fibrinogen/fibronectin binding to GPIIb/IIIa; SQ 29.548 as a TXA2 receptor antagonist; cyproheptadine as a serotonin receptor antagonist; BN 52021 as a platelet-activating factor receptor antagonist). The pattern of tyrosine-phosphorylated proteins, phosphorylation of initial lipids and phosphorylation of pleckstrin (P47) were used as markers for early signal transducing responses, while secretion of ADP+ATP and beta-N-acetyl-glycosaminidase were used as final responses. Intralipid showed no platelet activation except for some weak tyrosine protein phosphorylation that was inhibited by elevated cAMP. IEEC induced strong platelet activation that was partly inhibited by increased levels of cAMP and IAS. The inhibition of elevated cAMP seemed to be due to removal of the G protein-mediated activation from secreted autocrine stimulators either by IAS or forskolin. The remaining activity is a pure effect from IEEC which is not affected by elevated cAMP.

Adenosine Diphosphate↗
PubMed2001

Human hepatic stellate cells secrete adrenomedullin: potential autocrine factor in the regulation of cell contractility.

BACKGROUND/AIMS: Hepatic stellate cells (HSCs) are perisinusoidal pericytes which have receptors for vasoactive factors, such as endothelin-1, which can regulate cell contractility in an autocrine manner. It is unknown whether human HSCs have receptors for and are able to synthesize the vasodilator peptide adrenomedullin (ADM), a peptide produced by most contractile cells. METHODS AND RESULTS: Stimulation of HSCs with ADM resulted in a dose-dependent raise in cAMP concentration (radioimmunoassay) and markedly blunted the endothelin-induced increase in [Ca2+]i and cell contraction, as assessed in cells loaded with fura-2 using a morphometric method. The existence of the receptor CRLR for ADM and their associated proteins RAMP-1 and RAMP-2 was demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR). Moreover, activated human HSCs spontaneously secreted ADM in the culture medium in a time-dependent manner. ADM secretion was markedly enhanced by tumour necrosis factor-alpha and interleukin-1beta. Specific mRNA for ADM (RT-PCR and Northern blot) was detected in HSCs and increased after incubation of cells with cytokines. CONCLUSIONS: Human HSCs have functional receptors for ADM, the stimulation of which blunts the contractile effect of endothelin-1. Cultured human HSCs secrete ADM in baseline conditions. This secretion is markedly increased by cytokines. These results suggest that ADM can regulate HSCs' contractility in an autocrine manner.

Adrenomedullin↗
PubMed2000

Nicotine effects on proliferation and the bombesin-like peptide autocrine system in human small cell lung carcinoma SHP77 cells in culture.

OBJECTIVES: To determine whether nicotine affects the proliferation and expression of the bombesin-like peptide autocrine system in human small cell lung carcinoma (SCLC) SHP77 cells compared with nonmalignant human bronchial epithelial BEAS 2B cells as non-neuroendocrine controls. METHODS: Human lung cells were cultured in defined serum-free medium with various concentrations of nicotine added for various times. Proliferation was measured by cell counts and colorimetric assay, bombesin-like peptide receptor expression was assayed by specific binding assays and quantitative competitive PCR, and bombesin-like peptides determined by ELISA. RESULTS: Nicotine significantly stimulated the growth of human SCLC SHP77 and NCI-H865 cells, but not BEAS 2B cells. Bombesin-like peptide receptor specific binding and mRNA expression were not affected by nicotine exposure in SHP77 cells or BEAS 2B cells. An increase in SHP77 cellular bombesin-like peptide content was observed. CONCLUSIONS: Human SCLC SHP77 cells express the components of the bombesin-like peptide autocrine system. Increased proliferation in the presence of nicotine may be due in part to increased levels of bombesin-like peptides in SHP77 cultured in nicotine. Nicotine effects on nonmalignant pulmonary neuroendocrine cells may provide additional insight into how nicotine itself may promote lung carcinogenesis.

Binding, Competitive↗
PubMed2000

LPS stimulation of TNF-receptor deficient macrophages: a differential role for TNF-alpha autocrine signaling in the induction of cytokine and nitric oxide production.

To evaluate the role of autocrine TNF-alpha signaling in macrophage activation, immortalized macrophages from normal mice (B6/J2) and from mice containing gene targeted disruptions of the type 1 and type 2 TNF-receptor genes (TRN) were stimulated under CD14-dependent or serum-free conditions. Although the B6/J2 and TRN clones mounted similar nitric oxide responses to LPS in the presence of serum, the TRN macrophages responded poorly when stimulated with LPS under serum free conditions. LPS stimulation of TRN and B6/J2 under serum-free conditions resulted in equivalent levels of IL-1beta, TNF-alpha, and iNOS gene expression. However, Western blot analysis revealed that iNOS protein production by TRN was 2-fold lower than that produced by B6/J2. These results indicate that autocrine TNF-alpha stimulation contributes to the signaling pathways initiated by ligation of LPS receptors in the absence of LBP and is involved in iNOS post-transcriptional regulation.

Animals↗
PubMed1996

Autocrine mechanism of epidermal growth factor in choriocarcinoma cell proliferation.

We examined four choriocarcinoma cell lines, NaUCC-1, NaUCC-3, NaUCC-4 and BeWo, for the presence of epidermal growth factor (EGF) by enzyme immunoassay and reverse transcription and polymerase chain reaction, and for EGF receptor (EGFR) by 125I-EGF binding assay. Specific EGF binding and EGF proteins were detected in these four choriocarcinoma cell lines. On the cell lines examined, NaUCC-4 had the greatest EGF binding capacity (18 x 10(5) sites/cell) and the highest amount of immunoreactive EGF (142 pg/ml). These results prompted us to assess the significance of EGF/EGFR autocrine mechanism in NaUCC-4 cells. Low doses of exogenous EGF stimulated 3H-thymidine incorporation, and monoclonal antibodies against EGF or EGFR dose-dependently inhibited 3H-thymidine incorporation. On the other hand, these antibodies did not significantly affect hCG production. These results suggested that EGF might function in an autocrine manner to stimulate proliferation rather than differentiation of NaUCC-4 choriocarcinoma cells.

Adult↗
PubMed2000

Suppression of tumor growth by growth hormone-releasing hormone antagonist JV-1-36 does not involve the inhibition of autocrine production of insulin-like growth factor II in H-69 small cell lung carcinoma.

Although a high antitumor activity of growth hormone releasing hormone (GHRH) antagonists has been demonstrated in various tumors, the mechanism of action of these peptide analogs remains poorly understood. An association has been observed between the antitumor effects of GHRH antagonists and the inhibition of insulin-like growth factors (IGFs), but it is not clear whether the suppression of IGFs is obligatory for the action of GHRH antagonists. In the present study we investigated various components of the IGF system in H-69 small cell lung carcinoma (SCLC) xenografted into nude mice and treated with GHRH antagonist JV-1-36. After 31 days of treatment with JV-1-36, tumor weight was inhibited by about 70% as compared with the controls. Reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated that H-69 tumors express mRNAs for IGF-II and IGF-receptors- (IGFR-) I and II, but not for IGF-I. The levels of mRNA for IGF-II and IGFR-I and -II were not affected by the treatment with JV-1-36. Exposure to antibody IRa, which blocks the binding of IGF-I and -II to IGFR-I, inhibited the proliferation of H-69 cells in vitro, indicating that IGF-II present in the tumors might stimulate the proliferation of H-69 SCLC in an autocrine manner. Collectively our results suggest that inhibition of tumor growth by GHRH antagonists is not associated with the suppression of the autocrine stimulation by IGF-II in H-69 SCLC.

Animals↗
PubMed1997

The autocrine loop of TGF-alpha/EGFR and brain tumors.

Malignant human gliomas are the most common forms of primary tumors in the central nerve system. Due to their location and invasive nature, treatment so far has been mainly palliative. Thus, understanding the molecular detail of tumor transformation and progression is crucial for developing effective therapeutic strategy for this fetal tumor. Among the genetic alternations found in these tumors, p53 inactivation and PDGF/PDGFR activation represent the early events, and the loss of chromosome 10 and gene amplification and rearrangement of EGFR represent the late events. Studies with both glioma cell lines and primary tumor tissues have strongly suggested that TGF-alpha and EGFR function as an important autocrine loop in supporting proliferation of human glioma, especially in high grade glioma, since elevated TGF-alpha expression is also found in these high grade tumors. Furthermore, down regulation of the expression of TGF-alpha by antisense constructs has been shown to inhibit several types of human tumor cell growth including glioma. Other means of therapeutic approaches using this autocrine loop as a target also include the use of monoclonal antibodies and their cytotoxic conjugated. Considerable understanding of the EGFR-mediated signal transduction pathways has become available recently, which including GRB2/mSOS1 mediated MAP kinase activation; JAK/STATs pathway; PLC-gamma pathway. However, much work still needs to be done before a specific component of these pathways can be applied for effective control of tumor growth in the clinic.

Animals↗
PubMed1999

Autocrine motility factor (neuroleukin, phosphohexose isomerase) induces cell movement through 12-lipoxygenase-dependent tyrosine phosphorylation and serine dephosphorylation events.

Autocrine motility factor (AMF) is one of the motility cytokines regulating tumor cell migration, therefore identification of the signaling pathway coupled with it has critical importance. Previous studies revealed several elements of this pathway predominated by lipoxygenase-PKC activations but the role for tyrosine kinases remained questionable. Motility cytokines frequently have mitogenic effect as well, producing activation of overlapping signaling pathways therefore we have used B16a melanoma cells as models where AMF has exclusive motility effect. Our studies revealed that in B16a cells AMF initiated rapid (1-5 min) activation of the protein tyrosine kinase (PTK) cascade inducing phosphorylation of 179, 125, 95 and 40/37 kD proteins which was mediated by upstream cyclo- and lipoxygenases. The phosphorylated proteins were localized to the cortical actin-stress fiber attachment zones in situ by confocal microscopy. On the other hand, AMF receptor activation induced significant decrease in overall serine-phosphorylation level of cellular proteins accompanied by serine phosphorylation of 200, 90, 78 and 65 kd proteins. The decrease in serine phosphorylation was independent of PTKs, PKC as well as cyclo- and lipoxygenases. However, AMF induced robust translocation of PKCalpha to the stress fibers and cortical actin suggesting a critical role for this kinase in the generation of the motility signal. Based on the significant decrease in serine phosphorylation after AMF stimulus in B16a cells we postulated the involvement of putative serine/threonine phosphatase(s) upstream lipoxygenase and activation of the protein tyrosine kinase cascade downstream cyclo- and lipoxygenase(s) in the previously identified autocrine motility signal.

Actins↗
PubMed2003

Autocrine signalling through erbB receptors promotes constitutive activation of protein kinase B/Akt in breast cancer cell lines.

The protein kinase PKB/Akt plays a pivotal role in promoting cell survival and proliferation. This study investigated the regulation of PKB/Akt activity in breast cancer cells. In primary invasive breast cancers PKB/Akt exhibited elevated phosphorylation at regulatory site Ser473 in 80% of cases, using immunohistochemistry. The degree of phospho-PKB/Akt immunoreactivity was positively correlated with the extent of its nuclear accumulation. Moderate/strong staining was seen in 31% of the samples but was absent in tumour-associated normal breast epithelia. To examine the mechanisms of PKB/Akt activation, we studied its phosphorylation in a panel of breast cancer cell lines. PKB/Akt was constitutively phosphorylated on both regulatory sites (Thr308 and Ser473) in the absence of serum growth factors in 7 of 8 lines but not in two cell lines derived from normal breast epithelia. Further analysis revealed that constitutive PKB/Akt phosphorylation was associated with loss of PTEN phosphatase expression (CAL51, MDA-MB-468, BT549 cells) and constitutive activation of erbB2 (SKBR3, BT474 cells). In two further breast cancer lines (T47D and HS578T) PKB/Akt phosphorylation was dependent upon autocrine factors acting primary through the epidermal growth factor receptor (EGFR) and erbB2. Conditioned medium from HS578T cells stimulated EGFR-dependent PKB/Akt phosphorylation in normal breast cells. These results demonstrate that PKB/Akt is frequently activated in breast cancer through diverse mechanisms, including autocrine signalling via erbB receptors.

Breast Neoplasms↗
PubMed1994

Cyclosporin A inhibits growth of autocrine tumour cell lines by destabilizing interleukin-3 mRNA.

In T cells, cyclosporin A (CsA) exerts its immunosuppressive effect by preventing transcriptional induction of the expression of interleukin(IL)-2. This is achieved by a mechanism that involves binding of a CsA-cyclophilin complex to calcineurin, which in turn inhibits the phosphatase-controlled translocation of transcription factor NFAT to the nucleus. We have previously identified IL-3 as an autocrine oncogenic regulator in tumour cell lines generated by introducing the v-H-ras oncogene into IL-3-dependent mast cells. Here we report that CsA specifically blocks autocrine tumour cell growth. The mechanism involves down-regulation of IL-3 expression by destabilization of the messenger RNA and requires ongoing transcription. Transcripts from exogenous IL-3 genes lacking the (A+U)-rich element (ARE) in the 3' untranslated terminal repeat could not be destabilized, suggesting that at least part of this sequence, which is known to mediate decay of short-lived mRNA, participates in a CsA-sensitive regulatory mechanism.

Animals↗
PubMed1994

Distinct pathways for autocrine and paracrine Wingless signalling in Drosophila embryos.

Two secreted proteins, Wingless and Hedgehog, instruct cell fates within the segmented epidermis of Drosophila embryos (reviewed in ref. 5). Wingless (Wg) is expressed by the most posterior cells in each parasegment; Hedgehog (Hh) is expressed in the most anterior cells of the next parasegment. Immediately after gastrulation, the two cell types are mutually dependent. Local Wg signalling stabilizes Hh expression and local Hh signalling stabilizes Wg expression. Direct Wg autoregulation (autocrine signalling) is masked by its paracrine role in maintaining hh, which in turn maintains wg. I have used zeste-white3 (zw3) and patched (ptc) mutant backgrounds to uncouple genetically this positive-feedback loop and to study autocrine Wg signalling. I report here that direct Wg autoregulation differs from Wg signalling to adjacent cells in the importance of fused (fu), smoothened (smo) and cubitus interruptus (ci) relative to zw3 and armadillo (arm). I also find that Wg autoregulation during this early hh-dependent phase differs from later Wg autoregulation by lack of gooseberry (gsb) participation.

Animals↗
PubMed1995

A BDNF autocrine loop in adult sensory neurons prevents cell death.

During the initial phase of their development, sensory neurons of the dorsal root ganglion (DRG) require target-derived trophic support for their survival, but as they mature they lose this requirement. Because many of these neurons express BDNF (brain-derived neurotrophic factor) messenger RNA, we hypothesized that BDNF might act as an autocrine survival factor in adult DRG neurons, thus explaining their lack of dependence on exogenous growth factors. When cultured adult DRG cells were treated with antisense oligonucleotides to BDNF, expression of BDNF protein was reduced by 80%, and neuronal survival was reduced by 35%. These neurons could be rescued by exogenous BDNF or neurotrophin-3, but not by other growth factors. Similar results were obtained with single-neuron microcultures, whereas microcultures derived from mutant mice lacking BDNF were unaffected by antisense oligonucleotides. Our results strongly support an autocrine role for BDNF in mediating the survival of a subpopulation of adult DRG neurons.

Aging↗