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 829 records · Page 46Linked to original sources
PubMed1990

Identification of B16-F1 melanoma autocrine motility-like factor receptor.

B16-F1 melanoma cells express augmented glycosylation of a Mr 78,000 (gp78) cell surface glycoprotein in response to cell shape modulation which is correlated to an increased metastatic ability in vivo and motility in vitro. A monoclonal antibody (mAb) directed against gp78 was used to study its surface distribution and possible function in cell locomotion. On motile cells, gp78 is localized by immunofluorescence to the leading lamella as well as to the trailing edge, suggesting shuffling of gp78 during cell migration. When bound to the cells the mAb induced locomotory activity similar to the effect of the cells' autocrine motility-like factor (AMLF). The enhanced motility induced by either anti-gp78 mAb or autocrine motility factor (AMF) were both inhibited by pertussis toxin, indicating that the 3F3A mAb induces cell kinesis via the same pertussis toxin-sensitive G protein pathway as has been described for other motility factors. The binding of anti-gp78 mAb to its ligand was inhibited (10-fold) by preincubation with B16-F1 AMLF containing conditioned media. Based on such functional properties, it was concluded that gp78 behaves as an AMF receptor of the B16-F1 melanoma cell.

Animals↗
PubMed1990

Immunohistochemical evidence of autocrine growth factors in adenocarcinoma of the human lung.

We immunohistochemically examined 131 primary human lung adenocarcinomas for the possible presence of autocrine factors. Transforming growth factor alpha (TGF alpha) and epidermal growth factor (EGF) were considered growth factors with epidermal growth factor receptor (EGFR) as the receptor. Of these tumors, 87 (66%) showed a high expression of TGF alpha, 66 (50%) showed a high expression of EGF, and 55 (42%) were positive for EGFR reactivity. In the EGFR-positive cases, the 5-year survival rates of patients with high TGF alpha and low TGF alpha were 36% and 85%, respectively (P less than 0.05). The 5-year survival rates of patients with high EGF and low EGF were 25% and 77%, respectively (P less than 0.05). In contrast, in the EGFR-negative cases, there was no statistical difference between the 5-year survival rates of patients with either high TGF alpha or EGF and low TGF alpha or EGF. Because autocrine growth mechanisms are present in adenocarcinoma of the human lung, these events may contribute to clarification of tumor development, and perhaps even to a better prognosis.

Adenocarcinoma↗
PubMed1990

Coordinated induction of autocrine tumor necrosis factor and interleukin 1 in normal human monocytes and the implications for monocyte-mediated cytotoxicity.

Cytokine production and cytotoxicity for tumor cells are two important aspects of monocyte function and the inflammatory response against tumors and infectious agents. In the present studies we provide direct evidence at the mRNA and protein levels for the existence of autocrine tumor necrosis factor (TNF) and its importance as a mediator of human monocyte cytotoxicity for WEHI-164 tumor cells. The induction of TNF and interleukin 1 beta (IL-1 beta) mRNA by exogenous TNF or IL-1 beta, as determined by Northern blot analysis, is time dependent in normal human monocytes isolated by countercurrent elutriation. With either TNF or IL-1 beta as the stimulus, TNF mRNA is induced first, peaks within 1-3 h, and declines to nearly undetectable levels by 9 h. TNF mRNA accumulation is enhanced in the presence of cycloheximide indicating that de novo protein synthesis is not required for maximal TNF mRNA induction. In contrast, IL-1 beta mRNA is induced later, peaks at 3-9 h, and remains considerably elevated at 18 h. IL-1 beta mRNA accumulation is partially suppressed in the presence of cycloheximide. TNF and IL-1 beta protein production as assayed by specific enzyme-linked immunosorbent assays correlates well with respective mRNA induction. Both TNF and IL-1 beta enhance monocyte cytotoxicity as single agents; however, their combined effect is less than additive. When both agents are combined, TNF mRNA levels, as assessed by densitometric analysis of slot blots, are approximately equal to those induced by TNF alone. In contrast, IL-1 beta mRNA levels are additive. Our studies provide evidence for highly coordinated and interrelated pathways of autocrine TNF and IL-1 induction in human monocytes and demonstrate the role of TNF and IL-1 in regulating monocyte-mediated cytotoxicity for tumor cells.

Autoradiography↗
PubMed1990

Augmented MYCN expression advances the malignant phenotype of human neuroblastoma cells: evidence for induction of autocrine growth factor activity.

Amplification and enhanced expression of the MYCN oncogene are thought to contribute to the development and progression of human neuroblastomas. Here, we have transfected human neuroblastoma cells that harbor a single MYCN gene copy with the human MYCN gene driven by a viral enhancer/promoter, and we have compared the properties of the parental and the transfected cells. The transfected cells show an enhanced expression of the exogenous MYCN gene. Unlike the parental cells, they have acquired an increased proliferative potential, induce tumors in nude mice, grow in soft agar, and require low amounts of exogenous growth factors in order to proliferate. The MYCN-transfected, but not the parental, cells can synthesize and utilize autocrine growth factor activity. These results demonstrate that enhanced MYCN expression contributes to malignant progression of human neuroblastoma cells, conceivably by stimulating the expression of autocrine growth factor activity.

Animals↗
PubMed1989

Growth factors, oncogenes and the autocrine hypothesis.

Many aspects must be studied when considering theories of oncogenesis. Growth factors, the polypeptide hormones that are necessary for cell growth, and oncogenes, the genes that produce cancer, are only two aspects. Proto-oncogenes are found in normal cellular DNA and are believed to play regulatory roles in differentiation and development. Oncoviruses, mutation of DNA and chromosomal damage can activate proto-oncogenes and cause malignant change. Oncogenes can render transformed cells independent of growth factors. A cell can bypass the need for outside growth factors by producing the growth factor and its receptor, thereby using an autostimulatory impetus for growth. This is autocrine growth. An oncogene can also bypass the need for growth factors by activating or modifying growth factor receptors, or by stimulating intracellular events, such as tyrosine phosphorylation, both of which ultimately lead to cell division. The various mechanisms by which oncogenes act provide specific targets for treatment. Specific antigrowth factor or antireceptor antibodies or antagonists could interfere with autocrine regulation. Further research on the activation of oncogenes could provide valuable insight on regulation of the growth of tumors. Ultimately, the understanding of the molecular pathogenesis of cellular transformation will be a key to the prevention and treatment of cancer.

Cell Transformation, Neoplastic↗
PubMed1989

The growth of Rauscher erythroleukemia cells is mediated by autocrine production of a factor with biological activity similar to interleukin-3.

Under serum-deprived and chemically defined culture conditions, the growth of Rauscher erythroleukemia cells is mediated by an autocrine mechanism. The growth-promoting activity is produced by fresh or irradiated cells and resembles the activity of interleukin-3 (IL-3) in its ability to sustain colony formation from three of four IL-3-dependent cell lines and to induce formation of granulocyte/macrophage (GM) colonies and, in the presence of erythropoietin (Ep), of erythroid bursts and mixed erythroid colonies. IL-3, IL-1, IL-4, IL-6, GM colony-stimulating factor (GM-CSF), G-CSF, M-CSF, Ep, and media conditioned by concanavalin A-stimulated mouse spleen cells or phytohemagglutinin-stimulated LBRM 33 cells were unable to induce proliferation of the Rauscher erythroleukemia cells. Northern analysis of total and polyA-selected RNA extracted from untreated Rauscher cells or from cells 24 hours after irradiation showed the presence of message for M-CSF but not for IL-3, IL-1, GM-CSF, or G-CSF. The production of IL-6 was excluded by a sensitive bioassay. These results indicate that the autocrine growth of the Rauscher cell line is mediated by a growth factor different from IL-3, but with similar biological activity. Activation of the expression of such a growth factor during viral infection may contribute to the generation of leukemic cells that have the property to grow in vitro and generate Rauscher erythroleukemia cell lines.

Animals↗
PubMed1989

Paracrine rather than autocrine regulation of myeloma-cell growth and differentiation by interleukin-6.

To explore the mechanisms involved in the pathogenesis of human multiple myeloma (MM), we investigated the potential role of interleukin-6 (IL-6), a B-cell differentiation factor in humans, and a growth factor for rat/mouse heterohybridomas and murine plasmacytomas. Using a heterohybridoma assay, we found that two well-documented human myeloma cell lines, RPMI 8226 and U266, did not secrete IL-6 and did not express RNA messengers for IL-6. Neutralizing antibodies to IL-6 did not inhibit their proliferation, and recombinant IL-6 did not stimulate it. Taken together, these data show that IL-6 is not the autocrine growth factor of these human myeloma cell lines. A high production of IL-6 was found in the bone marrows of patients with fulminating MM, compared with patients with inactive or slightly active MM, or to healthy donors. This IL-6 production was assigned to adherent cells of the bone-marrow environment but not to myeloma cells. A spontaneous proliferation of myeloma cells freshly isolated from patients was observed in short-term cultures. Recombinant IL-6 was able to amplify it two- to threefold. The spontaneous proliferation of the myeloma cells was inhibited by anti-IL-6 antibodies and reinduced by recombinant IL-6. After 2 to 3 weeks of culture, the myeloma-cell proliferation progressively declined and no IL-6-dependent myeloma cell lines could be obtained despite repeated additions of fresh IL-6 and costimulation with other cytokines such as tumor necrosis factor (TNF)beta, or IL-1 beta. These data demonstrated a paracrine but not autocrine regulation of the growth and differentiation of myeloma cells by IL-6.

Aged↗
PubMed1989

Growth stimulation, altered regulation of epidermal growth factor receptors, and autocrine transformation of spontaneously transformed normal rat kidney cells by transforming growth factor beta.

The tumorigenic NRK-PT14 cell line requires exogenous epidermal growth factor (EGF), but has lost the requirement for transforming growth factor beta (TGF-beta) for anchorage-independent growth, compared to normal rat kidney (NRK) cells. Development of an optimized serum-free medium for the growth of these cells revealed that NRK-PT14 cells also exhibit a qualitatively altered sensitivity to exogenous type 1 TGF-beta, compared to NRK cells. EGF-induced serum-free monolayer growth of NRK-PT14 cells was stimulated 2-fold by TGF-beta under conditions where growth of NRK cells was inhibited by 67%. TGF-beta only stimulated the growth of NRK-PT14 cells when EGF was present and when EGF was added before TGF-beta. In addition, the stimulation of EGF-induced NRK-PT14 cell growth by TGF-beta was associated with a specific, reversible loss of the high-affinity subpopulation of EGF receptors from the surface of these cells. Treatment of NRK cells with TGF-beta resulted in an increase in this EGF receptor population. Finally, EGF-induced anchorage-independent growth of NRK-PT14 cells was shown to be dependent on secreted TGF-beta, demonstrating an autocrine role for TGF-beta in the transformed phenotype of these cells. Autocrine transformation of NRK-PT14 cells by TGF-beta may result directly from the acquisition of an altered (positive) sensitivity to this growth factor.

Animals↗
PubMed1989

[Endocrine, paracrine and autocrine factors in the maturation and functional development of the testis].

We have studied the specific effects of highly purified pituitary hormones on testicular cell multiplication and differentiation in the immature hypophysectomized rat. LH exhibits multiplicative effects on Leydig cells and, curiously, regressive effects on germ cells. Seminiferous tubules are the main site of action of FSH which induces direct differentiation of Sertoli cells and paracrine effects on germ cells resulting in their multiplication to the pachytene stage (in the absence of androgen). Through interstitium-directed paracrine effects, FSH promotes the differentiation of Leydig cells. Prolactin and lactogenic growth hormones are capable of exerting both differentiative and multiplicative effects on Leydig cells. The purity of the hormone preparations permit to define their specific and direct effects and those mediated by paracrine or autocrine factors synthetized locally under their control. Among these potential factors, we have demonstrated the pituitary-dependent expression of IGF-I, c-myc, c-fos proteins. The purity of the preparations used in this work permits to distinguish clearly the specific and direct effect of each pituitary hormone from those mediated by paracrine or autocrine factors.

Animals↗
PubMed1986

Autocrine growth of interleukin 2-producing leukemic cells in a patient with adult T cell leukemia.

Leukemic cells in the peripheral blood of a patient with adult T cell leukemia (ATL), which expressed the Tac antigen/interleukin 2 (IL2) receptor, were investigated in vitro for autocrine growth by IL 2. The cells showed spontaneous proliferation in mitogen-free medium. The spontaneous proliferation of the cells was inhibited by monoclonal anti-IL 2 or anti-Tac antibody. These cells were found to produce messenger RNA for IL 2 and secrete IL 2 during short-term culture in the same medium. Recombinant IL 2 and IL 2 secreted by the cells enhanced the proliferation of the cells in a dose-dependent manner when added to the initial culture. These findings demonstrate that an autocrine mechanism by IL 2 is involved in the proliferation of ATL cells during short-term culture.

Cell Cycle↗
PubMed1988

Autocrine growth of CD4+ T cells. Differential effects of IL-1 on helper and inflammatory T cells.

The growth factor requirements of cloned lines representing two major subsets of CD4+ T cells were examined. The helper subset, which produces IL-4 as its autocrine growth factor, proliferates in response to IL-2 or to IL-4 in the presence of IL-1. The inflammatory subset, which produces IL-2 as its autocrine growth factor, proliferates in response to IL-2 and, in the presence of limiting amounts of IL-2, shows increased proliferation in the presence of IL-4. The inflammatory subset does not proliferate in response to IL-1 plus IL-4. This ability to respond to the combination of IL-1 plus IL-4 correlates with the presence of IL-1R on the cloned lines tested. These data suggest that IL-1 may play a controlling role in the clonal expansion of CD4+ T cells of different functional types. This, in turn, suggests means by which the immune response could be directed into humoral or cell-mediated responses.

Animals↗
PubMed1988

cDNA clones from autocrine thymic lymphoma cells encode two mitogenic proteins, a serine protease and a truncated T-cell receptor beta-chain.

Cell lines derived from primary X-ray induced T cell lymphomas (PXTL) of C57BL/6 mice secrete into the medium factor(s) required for their growth. These autocrine factor(s) are distinct from previously described growth factors. cDNA cloning experiments were performed in an attempt to identify these autocrine factor(s). cDNA clones were selected by mRNA size, differential expression, and mitogenic activity of their translation products (Xenopus expression system) on PXTL cells. Two different cDNA clones yielded distinct mitogenic proteins. One clone encodes an altered form of the T cell receptor beta-chain which is truncated at the N-terminus to amino acid 49 of the constant region beta 2. The second clone encodes a serine protease which is identical to factor H or granzyme A from cytotoxic T cells. The 5' portion of the cDNA encoding the serine protease derived from PXTL cells differs from that derived from cytotoxic T cells. This difference results in distinct signal peptides. Unlike cytotoxic T cells, PXTL cells do not store the serine protease intracellularly but secrete it.

Amino Acid Sequence↗
PubMed1988

Transforming growth factor beta: potential autocrine growth inhibitor of estrogen receptor-negative human breast cancer cells.

Transforming growth factor beta (TGF beta), a two-subunit Mr 25,000 polypeptide, inhibits growth of several epithelial human cancer cell lines and has been proposed as an autocrine growth inhibitor. TGF beta activity has been found in conditioned media from some breast cancer cell lines, and TGF beta mRNA has been detected in breast cancer cell lines and human breast cancer specimens. In the present study we attempted to characterize the interaction of TGF beta with breast cancer cells by examining the biological activity, receptor binding, and secretion of this polypeptide by a panel of estrogen receptor (ER)-positive and ER-negative human breast cancer cell lines. Growth of the four ER-negative lines, MDA231, MDA330, HS578T, and BT20, was exquisitely sensitive to TGF beta. Dose-dependent inhibition of monolayer growth, anchorage-independent growth, and of [3H]thymidine incorporation was observed with TGF beta concentrations ranging from 1 to 100 pM. Growth of the four ER-positive lines, T47D, ZR75-1, and two MCF7 lines from different laboratories, was unaffected by similar concentrations of TGF beta. In receptor-binding studies using 125I-TGF beta, the four ER-negative lines exhibited specific high affinity TGF beta receptors. Binding was a time- and temperature-dependent process. Scatchard analysis of the binding data showed between 2800 and 12900 receptor sites per cell and a Kd between 29 and 160 pM. Epidermal growth factor, insulin, insulin-like growth factors I and II, and transforming growth factor alpha did not compete for 125I-TGF beta binding. Chemical cross-linking studies with ER-negative breast cancer cells revealed three specific TGF beta receptors with molecular weights approximating 400,000, 92,000, and 69,000. The four ER-positive lines had no detectable TGF beta binding. Using a radioreceptor assay with A549 cells and a NRK bioassay, TGF beta activity was detectable in the conditioned media from the four ER-negative cell lines; media from the ER-positive lines had low levels of TGF beta activity. In summary, ER-negative, estrogen-independent cultured human breast cancer cells have receptors for, are inhibited by, and secrete TGF beta activity, suggesting the possibility that this polypeptide may function as an autocrine growth inhibitor or as a paracrine growth factor for tumor stromal cells.

Affinity Labels↗
PubMed1986

B cell-derived BCGF functions as autocrine growth factor(s) in normal and transformed B lymphocytes.

This paper demonstrates that B cell lines, as well as normal activated B cells generate and respond to B cell-specific growth factor(s) (BCGF). BCGF derived from B cells (B-BCGF) appears to be distinct from interleukin 1, interleukin 2 (IL 2), B cell stimulatory factor, BCGF-II, interferon-gamma, or transforming growth factor. It acts on activated B cells, but not on resting G0 phase B cells to induce proliferation. B cell lines, immortalized by Epstein-Barr virus, constitutively secrete 10-fold higher level of B-BCGF compared with normal activated B cells, suggesting that an activated autocrine loop might be operating in immortalized B cells. On the basis of our observations, we postulate that B cell clonal expansion may occur, at least in part, through a B-BCGF-dependent autocrine pathway similar to IL 2 effect on T cells.

Adjuvants, Immunologic↗
PubMed1982

Autocrine secretion of peptide growth factors by tumor cells.

Transforming growth factors (TGF) are growth-promoting polypeptides that cause phenotypic transformation and anchorage-independent growth of normal cells. They have been isolated from several human and animal carcinoma and sarcoma cells. One TGF is sarcoma growth factor (SGF) which is released by murine sarcoma virus-transformed cells. Whereas the TGF interacts with epidermal growth factor (EGF) cell membrane receptors, it is not detectable in culture fluids from cells which contain high numbers of free EGF cell membrane receptors. The SGF acts as a tumor promoter in cell culture systems, and its effect on the transformed phenotype is blocked by retinoids (vitamin A and synthetic analogs). The production of TGF by transformed cells and the responses of normal cells to the addition of TGF to the culture medium raise the possibility that cells "autostimulate" their growth by releasing factors that rebind at the cell surface. The term "autocrine secretion" has been proposed for this type of situation in which a cell secretes a hormone-like substance for which it has external cell membrane receptors. The autocrine concept may provide a partial explanation for some aspects of tumor cell progression.

Animals↗
PubMed1994

CD40 expression in malignant plasma cells. Role in stimulation of autocrine IL-6 secretion by a human myeloma cell line.

Myeloma is a neoplasia characterized by the accumulation of malignant plasma cells in the bone marrow. In these studies, we have demonstrated that CD40 is expressed in human myeloma cells and have used a recently established IL-6-dependent myeloma cell line, ANBL-6, to examine the potential function of CD40 expression in myeloma cells. In addition to its expression on the ANBL-6 cells, we show that CD40 is expressed on freshly isolated myeloma cells from seven of seven patients tested. To address the role of CD40 expression in myeloma cells, we have examined the responsiveness of the ANBL-6 cell line to a CD40-specific mAb, G28-5. This cell line has previously been shown to proliferate only in response to IL-6. Of interest in this study, G28-5 also induced proliferation of the ANBL-6 cells. This proliferation was substantially inhibited by an IL-6-neutralizing mAb. Analysis of ANBL-6 cell culture supernatants by ELISA demonstrated that G28-5-stimulated cells secreted significant levels of IL-6, whereas unstimulated cell culture supernatants contained undetectable levels of IL-6. Furthermore, CV-1/EBNA cells expressing the human CD40 ligand also induced the proliferation of the ANBL-6 cell line, an effect that was inhibited by the anti-IL-6 mAb. Lastly, RNA blot analysis demonstrated an increase in IL-6 message in G28-5-stimulated ANBL-6 cells over unstimulated cells. These results indicate that the primary mechanism of anti-CD40-stimulated proliferation of the ANBL-6 cells is the induction of autocrine IL-6 production. Moreover, these data suggest that the expression of CD40 in malignant plasma cells may play a role in tumor cell expansion, possibly by stimulating the induction of autocrine IL-6 secretion.

Antibodies, Monoclonal↗
PubMed1994

Murine myeloid cells transformed by myb require fibroblast-derived or autocrine growth factors in addition to granulocyte-macrophage colony-stimulating factor for proliferation.

Murine myeloid cells can be transformed in vitro by infection with recombinant retroviruses carrying activated myb genes. While these myb-transformed hematopoietic cells (MTHCs) can proliferate continuously in culture, they exhibit several characteristics of progenitor cells of the granulocyte-macrophage (GM) lineage, including an absolute dependence on hematopoietic growth factors (HGFs) such as GM colony-stimulating factor (GM-CSF) for survival and growth. Whereas we have previously shown that MTHCs respond synergistically to certain combinations of HGFs, we report here that MTHCs apparently require two HGFs for proliferation, because GM-CSF alone appears insufficient to promote growth when MTHCs are cultured at very low densities. However, proliferation can be stimulated by either increasing the density at which MTHCs are cultured (implying the production of an autocrine growth factor) or by the presence of a feeder layer of irradiated fibroblasts. We find that the activity of such feeder layers is greatest when the MTHCs are allowed to contact them directly; and by using mutant fibroblast lines, that it depends on the production of CSF-1, but not Steel factor (SLF). In contrast, the autocrine factor appears not to be either CSF-1 or SLF, and the possibility is raised that it may represent a novel HGF activity. Potential implications of these results for normal and leukemic hematopoiesis are discussed.

Animals↗
PubMed1994

Platelet-activating factor mediates an autocrine proliferative loop in the endometrial adenocarcinoma cell line HEC-1A.

We investigated the synthesis and biological effects of platelet-activating factor (PAF) in the human endometrial cancer cell line HEC-1A. We found that HEC-1A cells actively synthesize and release PAF, as demonstrated by both [3H]acetate incorporation into PAF and gas chromatography-mass spectrometry studies. HEC-1A cells not only synthesize but also respond to PAF. Indeed, in fura-2-loaded cells, PAF stimulates [Ca2+]i increase with a median effective concentration of 5.6 nM. Furthermore, PAF induces a time-dependent expression increase of the nuclear protooncogene c-fos with a median effective concentration of 130 nM and stimulates DNA synthesis (median effective concentration, 700 nM). All of these effects are inhibited by the PAF receptor antagonist L659,989. Radioligand binding studies indicated the presence of two populations of PAF receptors with affinity constants in the nanomolar and micromolar range. Since the PAF antagonist per se inhibits DNA synthesis and cell proliferation, we suggest that PAF supports an autocrine growth circuit in HEC-1A cells. On the contrary, in the uterine leiomyosarcoma cell line SK-UT-1, which does not express specific binding sites for PAF, neither this phospholipid nor its receptor antagonist affect DNA synthesis. Our results provide evidence for the existence of an autocrine proliferative loop involving PAF in the endometrial cancer cell line HEC-1A.

Acetyl-CoA C-Acetyltransferase↗