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)

Damage to the breast epithelium by chemical carcinogens as products of oxygen free radical release can lead to fibroblast proliferation, hyperplasia of epithelium, cellular atypia and breast cancer. Chemical carcinogens may accumulate in breast fluid in the non-lactating breast consequent to superoxide free radical production which occurs via the adenosine triphosphate (ATP) hypoxanthine pathway. This pathway is initiated by hypoxia of local tissue. Under hypoxic conditions ATP is broken down to form hypoxanthine. Hypoxanthine itself is broken down to produce xanthine and then uric acid. This results in the production of superoxide free radicals, the products of which are carcinogenic. The development of localized hypoxia, which is central to this hypothesis, is caused by acinal gland distention from fluid secreted by raised prolactin levels in the absence of oxytocin. Stimulation of the nipple in a non-lactating breast may raise plasma oxytocin and lower plasma prolactin levels. Contraction of the myoepithelial cells of the breast under the influence of oxytocin would relieve distention of the acinal glands and thus reduce hypoxia and the generation of lipid peroxidoses as products of free radical damage. The epidemiology of breast fibrosis and cancer support the notion that lack of nipple stimulation over time may be a significant variable. A review of this literature linked with current biochemical work on fibrosis and carcinogenesis suggest that draining the breasts of the products of superoxide free-radical release by the encouragement of regular nipple erections may prevent such breast disease.
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PMID:Epidemiological and biochemical support for a theory on the cause and prevention of breast cancer. 180 62

The development of the human breast is dependent on the presence of ovarian steroids. The basic secretory units--the alveoli--continue to respond to steroids throughout the reproductive years. Lactogenesis is triggered by a rapid and drastic fall in progesterone at delivery and maintained by prolactin while the actual expulsion of milk from the breast depends on oxytocin. The composition of milk is very variable but is adequate to provide the sole source of nutrients for up to the first 6 months of life. Lactation suppresses ovarian activity probably through a disturbance in the pulsatile pattern of LH secretion but the degree of suppression depends on infant feeding patterns and perhaps on maternal nutritional status. Breastfeeding therefore confers a degree of protection against pregnancy but some artificial methods of contraception are appropriate for use during lactation. It is still not clear whether breastfeeding protects significantly against breast cancer.
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PMID:Physiology of lactation. 224 1

Table 2 summarizes the proven and potential uses of anti-progesterones in obstetrics and gynaecology. In addition to their role in the induction of menstruation and the interruption of first-trimester pregnancy, anti-progesterones can definitely accelerate cervical ripening and promote the termination of second-trimester pregnancy, especially in combination with exogenous prostaglandins. Furthermore, anti-progesterones can also initiate labour in the obstetric complication of fetal death in utero, leading to delivery of the fetus and placenta without additional medical treatment and without surgery in the majority of patients. The wider use of anti-progesterones for the induction of labour, with or without other adjuvants such as oxytocin or prostaglandin analogues, is still uncertain and awaits further study. Anti-progesterones may also be useful in the medical treatment of early ectopic pregnancy, either alone or in combination with other medicines. Preliminary results indicate that progesterone receptor antagonists may also be useful both for the initiation and promotion of lactation as well as the possible management of advanced breast cancer containing progesterone receptors. Finally, the usefulness of anti-progesterones in other gynaecological malignancies containing progesterone receptors, such as endometrial or ovarian cancers, awaits further study.
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PMID:Anti-progesterones in obstetrics, ectopic pregnancies and gynaecological malignancy. 306 66

The non-steroidal antioestrogen tamoxifen (trans-1-(4-beta-dimethylaminoethoxyphenyl)-1,2-diphenylbut- 1-ene), widely used in the treatment of breast cancer, and its oestrogenic cis-isomer rapidly inhibited contractile responses of isolated rat myometrium to supramaximal concentrations of oxytocin (1.28 X 10(-6) mol/l). Both compounds were effective at concentrations comparable with the plasma concentrations of tamoxifen reached in therapy (i.e. 5 X 10(-7) to 5 X 10(-6) mol/l). Inhibition was too rapid in onset (less than 3 min) to involve changes in RNA transcription and protein synthesis, and was not prevented or reversed by the addition of oestradiol to the bath. We conclude that the inhibition did not involve the classical oestrogen receptor pathway. Oestradiol-17 beta at concentrations above 10(-6) mol/l also inhibited the myometrium and potentiated the effects of the anti-oestrogens. Our experiments suggest that the anti-oestrogens and oestradiol act via a similar route with tamoxifen having an equilibrium affinity approximately tenfold greater than that of oestradiol.
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PMID:Acute inhibition of rat myometrial responses to oxytocin by tamoxifen stereoisomers and oestradiol. 650 64

Immunohistochemical analysis for products of vasopressin and oxytocin gene expression was performed on acetone-fixed tissues from 19 breast cancers representing a variety of tumor sub-types. Studies employed the avidin-biotin complex (ABC) immunohistochemical procedure and utilized rabbit polyclonal antibodies to arginine vasopressin (VP), provasopressin (ProVP), vasopressin-associated human glycopeptide (VAG), oxytocin (OT), oxytocin-associated human neurophysin (OT-HNP), and a mouse monoclonal antibody to vasopressin-associated human neurophysin (VP-HNP). Western Blot analysis was performed on protein extracts of fresh-frozen tissues from 12 additional breast tumors. While VP gene related proteins were not detected in normal breast tissue, immunohistochemistry revealed the presence of VP, ProVP, and VAG in all neoplastic cells for all of the tumor tissues examined. Vasopressin-associated human neurophysin was evident in only one of 19 acetone-fixed tumor preparations. However, Western blot analysis for all 12 fresh-frozen tumor samples showed the presence of two proteins, 42,000 and 20,000 daltons, that were immunoreactive with antibodies to VP, VP-HNP, and VAG. Oxytocin and OT-HNP, by immunohistochemistry, were found to be common to cells of normal breast tissues. For tumors, positive staining for OT was observed in 8 of 18 tumors, while OT-HNP was not detected in any of the tumors examined. These findings indicate that VP gene expression is a selective feature of all breast cancers, and that products of this expression might therefore be useful as markers for early detection of this disease and as possible targets for immunotherapy.
Breast Cancer Res Treat 1995 Jun
PMID:Vasopressin gene related products are markers of human breast cancer. 757 87

This hypothesis proposes that carcinogens in the breast are generated by the action of superoxide free radicals released when acinal gland distension, under the influence of unopposed prolactin, causes microvessel ischaemia. Inadequate nipple care in the at-risk years leads to ductal obstruction preventing the elimination of carcinogens from the breast. The regular production of oxytocin (OT) from nipple stimulation would cause contraction of the myoepithelial cells, relieving acinal gland distension and aiding the active elimination of carcinogenic fluid from the breast. Mechanical breast pump stimulation causes an increase in plasma OT levels in the luteal but not in the follicular phase of the menstrual cycle. OT production upon nipple stimulation in the luteal phase of premenopausal, non-lactating women may be protective against the high rates of mitotic breast cell division noted at this time via the potential to block the effect of oestrogen. The epidemiology of breast cancer suggests that lengthy lactation time is beneficial. Sexual activity in nulliparous women also protects and OT levels have been shown to rise with orgasm in women and in men. OT systems in the brain are intricately linked to oestrogen and progesterone levels, and it is possible that these hormones may modify the OT secretory response both centrally and through an effect on the sensitivity of the breast. OT production with nipple care and in sex and lactation, and the reduction in cycling ovarian hormones that occurs with pregnancy, may all be important preventative factors in the development of breast cancer both pre- and post-menopausally.
Breast Cancer Res Treat 1995 Aug
PMID:The potential for oxytocin (OT) to prevent breast cancer: a hypothesis. 764 45

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

Recent evidence indicates that oxytocin (OT), in addition to the induction of myometrial and myoepithelial cell contraction, can influence proliferation and differentiation in developing mammary glands and in breast cancer cells, hence the interest in detecting and locating OT receptors (OTRs). We produced rabbit antisera and a monoclonal antibody against a synthetic peptide corresponding to the carboxy terminus of the predicted OTR sequence. We tested their specificity in immunoblasts and immunocytochemical tests. All of the antibodies specifically stained myometrium (at term of pregnancy). In the human breast, OTRs were detected in myoepithelial cells along ducts of normal lobules and in sclerosing adenosis. Intraductal cells in benign hyperplastic lesions were also positive. OTRs were demonstrated in cases of primary and metastatic carcinomas of the breast. In the same tissues, OTR gene expression was shown by reverse transcriptase polymerase chain reaction procedures detecting the specific mRNA. These results suggest that the interaction between OT and its receptors might play a role in the origin and evolution of non-neoplastic lesions and carcinomas of the breast.
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PMID:Immunolocalization and gene expression of oxytocin receptors in carcinomas and non-neoplastic tissues of the breast. 866 75


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