Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to isolate and characterize genes whose expression may be altered in breast malignancy, we screened a cDNA library with a polyclonal anti-serum against breast-cancer-metastasis membranes and isolated several immunopositive clones. One of these, AJ1, was analyzed in detail and found to be expressed at varying levels as a 3.3-kb mRNA in all of 143 breast cancers. High expression was associated with lymph-node involvement (p = 0.03). Comparison between high- and low-expressing groups showed a significant difference at 4 and 6 years for both overall (p = 0.004 and p = 0.002 respectively) and disease-free (p = 0.0001 and p = 0.04 respectively) survival, but not at 11 years. AJ1 was expressed at much lower levels in non-malignant biopsies as compared with malignant tissue (p = 0.001). Expression was observed in breast-cancer cell lines MCF-7, ZR-75-1, T47D, MDA-MB-231 and HBL 100. Partial sequence analysis of the 620 bp clone showed complete homology with human heat-shock protein 89 alpha. In addition to being heat-inducible in all the breast cell lines examined, AJ1 levels were increased by estradiol (blocked by cyclohexamide and tamoxifen), EGF, oxytocin and vasopressin in a time-dependent manner in MCF-7 cells and by estradiol, EGF, prolactin and hydrocortisone in T47D cells. In MDA-MB-231 cells, EGF caused down-regulation of AJ1 mRNA levels. The increasing evidence for the association of heat-shock proteins with steroid receptors suggests that AJ1 may play an important role in the control of estrogen-receptor transcriptional activity in breast cancers.
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PMID:Clinical and biological significance of HSP89 alpha in human breast cancer. 173 10

In this study we show that treatment of MDA-MB231 hormone-independent human breast cancer cells with oxytocin (OT) or with the OT analogue F314 induces significant growth inhibition together with a change in cell phenotype. In MCF7 and T47D human breast cancer cells, OT inhibits oestrogen-induced cell growth. In these same cells, OT administration significantly enhances the inhibitory effect of tamoxifen on cell proliferation. MDA-MB231, MCF7 and T47D cells all express mRNA specific for the OT receptor. These data suggest that it may be possible to inhibit breast cancer growth using OT and OT analogues.
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PMID:Oxytocin inhibits proliferation of human breast cancer cell lines. 785 70

The expression of the oxytocin (OT) receptor (OTR) in breast cancer was studied using newly established anti-OTR monoclonal antibodies. Immunoblotting indicated that the antibody 2F8 recognized a 70K OTR in the pregnant myometrium and breast cancer tissue. Among 57 breast cancer patients, we detected OTR immunoreactivity in 52 (91.2%) by immunohistochemistry using 2F8. Using another monoclonal antibody for different receptor domains, 1-2, the staining profile was identical in all positive samples. Of 52 OTR-positive samples, 28 were diffusely positive (> 80% of cancer cells were stained), and 24 were partially positive (< 80% cells were stained). The ratio of estrogen receptor-positive samples was slightly higher among those that were diffusely positive, but there was no apparent relationship between OTR expression and other clinical parameters. We also confirmed the expression of the OTR in positively stained samples by means of Northern blotting and RT-PCR at the transcription level. The OTR messenger RNA and RT-PCR product were the same size as those in the pregnant myometrium. We also determined the expression of the OTR using flow cytometry in four breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-361, and MDA-MB-468). However, OT had no significant effect on their growth during a short period (7 days) of culture. These findings indicated that the OTR is expressed in breast cancer derived not from the myoepithelium but from the glandular or ductal epithelium; however, the biological function of OT in breast cancer remains to be determined.
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PMID:Investigation of the oxytocin receptor expression in human breast cancer tissue using newly established monoclonal antibodies. 859 29

The effects of oxytocin (OT) and the OT-analogue F314 were investigated an xenografts of mouse mammary and colon carcinomas (TS/A and C26 tumors) and of rat mammary carcinoma (D-R3230AC). In all cases, proliferation was previously assessed by cell counting in cultured cell lines, whereas tumor growth was checked by serial measures of tumor volume and by evaluation of tumor weight at the end of the experiment. Both cell proliferation and tumor growth were inhibited by OT and F314. These data support previous observations on the inhibitory effect of OT and F314 on the growth of MCF7, T47D and MDA-MB231 human breast cancer cell lines and open new prospects for testing the effect of this hypothalamic hormone and its analogues on the control of breast carcinoma growth.
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PMID:Oxytocin and oxytocin-analogue F314 inhibit cell proliferation and tumor growth of rat and mouse mammary carcinomas. 864 55

Oxytocin (OT) inhibits the proliferation of breast-cancer cells in vitro via a specific G-coupled receptor. To elucidate the intracellular mechanism involved in this biological effect, different G-coupled receptor mediators have been investigated in untreated and OT-treated MDA-MB231 breast-carcinoma cells. In these cells, after OT treatment, a significant cAMP increase was observed using a radioimmunoassay procedure, whereas the Ca2+ (determined with the fluorescent probe fura-2) and the inositol phosphate (determined after cell labeling with myo(2-(3)H)-inositol) concentrations were not modified, contrary to what has been observed in myometrial and myo-epithelial cells. The PKA inhibitor PKI (6-22) amide reverted the effect of OT, indicating that the anti-proliferative effect of the peptide is strictly related to the cAMP-PKA pathway. OT treatment did not modify tyrosine phosphorylation either. Our results indicate that in breast epithelial cells devoid of contractile activity, cAMP is the intracellular mediator of OT action, whereas the Ca2+-phosphoinositide system is not involved.
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PMID:Oxytocin inhibits the proliferation of MDA-MB231 human breast-cancer cells via cyclic adenosine monophosphate and protein kinase A. 921 43

In the present work, first we reviewed and completed our previous experiments on the antiproliferative effect of oxytocin (OT) in breast cancer cell lines. In vitro, OT 10 nM and 100 nM inhibited cell proliferation of MDA-MB231 (human breast carcinoma) and TS/A (mouse mammary carcinoma) cell lines. In vivo, OT significantly reduced the growth of TS/A mammary tumors. Both effects are mediated by specific receptors (OTR) distributed on cell surface. Second, using immunohistochemistry and RT-PCR we detected OTR and OTR mRNA in normal and pathological breast tissue. There is no correlation among OTR presence in breast carcinomas and the age of patients, tumor stage, estrogen receptor positivity, oncogene expression and proliferation rate of the same tumor. On the contrary, progesterone and OTR expression are correlated. These data confirm our previous evidence of a role of OT and OTR in normal and neoplastic breast cells.
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PMID:Oxytocin receptor within the breast: biological function and distribution. 970 81

Research suggests that oxytocin acts as a growth modulating agent for breast cancer cells. However, the signaling mechanisms responsible for these modulatory effects have not been fully elucidated. In the physiological setting oxytocin is known to stimulate contraction of myometrial cells in the uterus and myoepithelial cells in the breast by increasing intracellular free calcium ([Ca2+]i). The expression of oxytocin receptor mRNA in T-47D breast cancer cells, and four additional breast cancer cell lines (BT-549, MCF-7, MDA-MB- 231, ZR-75-1), was confirmed by RT-PCR analysis. Oxytocin-induced changes in [Ca2+]i in indo-1 AM loaded T-47D breast cancer cells were monitored using flow cytometric analysis. In this cell line, oxytocin (0, 1, 10, 100, and 1,000 nM) did not induce a dose-dependent increase in the mean 405 nm/485 nm emission ratio. These results indicate that oxytocin signaling in T-47D breast cancer cells does not appear to involve an increase in [Ca2+]i.
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PMID:Oxytocin does not induce a rise in intracellular free calcium in human breast cancer cells. 1046 79

Platelet-activating factor (PAF), a phospholipid mediator of inflammation, is present in breast cancer tissue and correlates with microvessel density. In the present study, we investigated the biological significance of PAF synthesized within breast cancer. In vitro, we observed the production of PAF by two estrogen-dependent (MCF7 and T-47D) and an estrogen-independent (MDA-MB231) breast cancer cell lines after stimulation with vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor, tumor necrosis factor, thrombin but not with estrogen, progesterone, and oxytocin. The sensitivity to agonist stimulation and the amount of PAF synthesized as cell-associated or released varied in different cell lines, being higher in MDA-MB231 cells, which are known to be highly invasive. We further demonstrate, by reverse transcriptase-polymerase chain reaction and cytofluorimetry, that all of the breast cancer cells express the PAF receptor and respond to PAF stimulation in terms of proliferation. Moreover, in MDA-MB231 cells PAF elicited cell motility. In vivo, two structurally different PAF receptor antagonists WEB 2170 and CV 3988 significantly reduced the formation of new vessels in a tumor induced by subcutaneous implantation of MDA-MB231 cells into SCID mice. In conclusion, these results suggest that PAF, produced and released by breast cancer cells, can contribute to tumor development by enhancing cell motility and proliferation and by stimulating the angiogenic response.
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PMID:PAF produced by human breast cancer cells promotes migration and proliferation of tumor cells and neo-angiogenesis. 1107 30

In vivo there appears to be a marked association between oestrogen levels and the expression of the oxytocin (OT) gene in most tissues. Transfection and DNA-protein binding experiments using high levels of either oestrogen receptor (ER)alpha or ERbeta imply a direct interaction of these transcription factors with the multiple hormone response element (HRE) at approximately -160 from the transcription start site of the OT gene in most species. In an extensive set of experiments, we show, using both transfection and protein-DNA binding, that low to moderate amounts of either oestrogen receptor, while being able to interact directly with a classic oestrogen response element (ERE) fail to interact with the human OT -160 HRE. Instead, this element, similar to its bovine counterpart, has a high affinity for the orphan receptors steroidogenic factor 1 and chicken ovalbumin upstream promoter transcription factor. Second, the human and bovine OT promoter can be made artificially responsive towards oestrogen in a cotransfection system over-expressing ERalpha or ERbeta, but not in cells expressing natural levels of these steroid receptors. Interestingly, nuclear extracts from both ERalpha-positive MCF7 cells and ERalpha-negative MDA-MB231 cells both contain a transcription factor which binds specifically to both the hOT-HRE element and to a classic ERE, and which has orphan receptor-like binding properties rather than those of an oestrogen receptor. Together, these and other results suggest that oestrogen action in vivo on the OT gene in all species is more likely to involve a DNA-independent mechanism than classic direct interactions with dimeric oestrogen receptors.
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PMID:The affinity and activity of the multiple hormone response element in the proximal promoter of the human oxytocin gene. 1204 22

Transcriptional activation of the gene coding for the neuropeptide hormone oxytocin by oestrogens does not follow the classical model of oestrogen receptor action. The oxytocin promoter does not contain an oestrogen response element (ERE), but instead a high-affinity binding site for nuclear orphan receptors. In the present study, the oestrogen-dependent up-regulation of the bovine oxytocin promoter is investigated in MDA-MB 231 cells. Control by oestrogen is shown to be dependent on the integrity of the nuclear orphan receptor binding site and the presence of ligand-activated oestrogen receptor, but independent of oestrogen receptor binding to DNA. Partial agonists tamoxifen and raloxifen and the pure antagonist ICI 182 780 all show agonistic activities on transcription, while exhibiting normal binding affinities to oestrogen receptor (ER)alpha. Nuclear orphan receptors oestrogen receptor-related receptor alpha (ERRalpha) and germ cell nuclear factor (GCNF) are expressed to significant levels in MDA-MB 231 cells. Binding of ERRalpha to the oxytocin promoter binding site can be demonstrated, suggesting the involvement of this nuclear orphan receptor in oestrogen-dependent up-regulation. The oestrogenic stimulation of the oxytocin promoter apparently is dependent on the stimulation of the transcriptional activity of this nuclear orphan receptor by ERK-1/ERK-2 mitogen-activated protein kinases (MAP kinases). This novel nonclassical mechanism of oestrogen action most probably is not restricted to the regulation of neuropeptide hormone expression, but may further contribute to the multitude of tissue-specific effects of oestrogenic substances.
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PMID:Transcriptional activation of the oxytocin promoter by oestrogens uses a novel non-classical mechanism of oestrogen receptor action. 1584 31


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