Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

pS2 protein expression has been demonstrated in a range of malignant tissues in an oestrogen-independent pathway. Recently, it has been demonstrated that pS2, in prostate cancer, is closely associated with neuro-endocrine differentiation. In the present study, we have analyzed, by immunohistochemistry along with microwave antigen retrieval, the expression of pS2 protein in a retrospective series of 236 human primary neuro-endocrine tumours and attempted to correlate this with the clinicopathologic features of patients and the presence of oestrogen receptor (ER). pS2 immunoreactivity was detected in 42% of small-cell lung carcinomas, 36% of lung carcinoids, 33% of phaeochromocytomas, 38% of carotid-body tumours, 31% of pancreatic neuro-endocrine tumours, 60% of stomach carcinoids, 55% of ileal carcinoids, 23% of appendiceal carcinoids and 86% of rectal carcinoids respectively in more than 10% tumour cells. No pituitary tumours displayed pS2 immunoreactivity. pS2 transcript was also detected in lung carcinoid and carotid-body tumours by Northern-blot analysis. There was a statistically higher incidence of pS2 expression in carcinoid tumours of the ileum and rectum than in those of the appendix. No association was observed between pS2 expression and the occurrence of the carcinoid syndrome; nor was any correlation observed between the occurrence of pS2 immunoreactivity and that of ER. Our results suggest that the expression of the pS2 protein in a wide spectrum of neuro-endocrine tumours may be implicated in the pathogenesis and progression of some neuro-endocrine tumours in an oestrogen-independent pathway.
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PMID:Expression of a breast-cancer-associated protein (pS2) in human neuro-endocrine tumours. 922 3

Expression of pS2, an oestrogen-regulated gene, has been associated with a good short-term prognosis and response to endocrine therapy. The aim of this study was to determine whether expression of mRNA for the pS2 gene in breast cancer could contribute useful information on disease behaviour and survival at medium-term follow-up. Northern blotting was used to detect pS2 messenger ribonucleic acid (mRNA) in the primary tumour tissue from each of 90 patients with breast cancer. Axillary node status was established by sampling or clearance, oestrogen receptor concentration by enzyme immunosorbant assay and follow-up was continued for at least 6 years or until death. At 83 months mean follow-up, 29 of 90 (32%) patients had recurrent disease and, of these, 18 (20%) had died from breast cancer. pS2 mRNA expression, present in 26 of 90 (29%) cancers, was associated with freedom from disease recurrence (P = 0.026) and was significantly associated with survival at a minimum of 6 years follow-up (P < 0.001). Pathological node status and tumour size were also significantly associated with disease recurrence (P < 0.001 and P = 0.002 respectively) and inversely with survival (P < 0.001 and P < 0.001 respectively). After multiple Cox regression analysis, pS2 expression was still a significant predictor of recurrence (but not survival) after adjusting for node status and tumour size; oestrogen receptor was an independent predictor of survival. The combination of node status and pS2 expression discriminated patients with particularly good prognosis (node negative, pS2 positive: no mortality at 6 years) or poor prognosis (node positive, pS2 negative; 41% mortality at 6 years). Evaluation of pS2 expression in breast cancer at diagnosis may provide additional useful prognostic information to conventional staging.
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PMID:PS2 mRNA expression adds prognostic information to node status for 6-year survival in breast cancer. 947 49

Since there is a preponderance of large bowel cancer in males, both in humans and in experimental models, and hormone replacement therapy is protective, a role for sex steroid hormones in the pathogenesis of this neoplasm seems likely. Evidence of functional oestrogen receptor has been looked for in large bowel mucosa and cancer. Expression of oestrogen receptor, and of the oestrogen-inducible receptor-associated genes pS2 and ERD5, was sought. Oestrogen receptor mRNA was detected in cancers and paired normal mucosae in equal amounts. In situ hybridization identified stromal cells above the muscularis mucosae that were positive for oestrogen receptor mRNA. pS2 mRNA was also detected, with a signal intensity significantly higher in normal mucosa compared with cancers, whereas the reverse was seen with ERD5 mRNA levels. pS2 and ERD5 were expressed in epithelium, with the former in a greater amount in distal colon and rectum than proximal colon. Although oestrogen-inducible and receptor-associated genes are expressed in large bowel mucosa, their expression does not correlate with oestrogen receptor.
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PMID:Expression of oestrogen receptor and oestrogen-inducible genes pS2 and ERD5 in large bowel mucosa and cancer. 960 6

The in vitro effects of two closely related phyto-oestrogens daidzein and equol on the oestrogen receptor positive human breast cancer cells MCF-7 were examined. There is differential metabolism of daidzein in humans, and the conversion of daidzein to equol by intestinal microbes occurs only in 30% of the population. The differential potency of these two compounds is thus of considerable importance since it may be likely that the relative risk of hormone-dependent cancers may be higher in 'non-responders'. In the present study, we compared the ability of both these compounds to induce mRNA expression of the oestrogen-responsive pS2 gene, to compete with oestradiol for binding to the oestrogen receptor (ER) and to affect cellular proliferation. Our studies demonstrate that equol is a 100-fold more potent than daidzein in stimulating an oestrogenic response. Equol was also more effective than daidzein in competing with 3H-oestradiol for binding to the ER. These results suggest that equol has a higher affinity for the ER. Both compounds stimulated the growth of MCF-7 cells in a concentration-dependent manner (10(-8)-10(-5)M). Although equol exhibits oestrogenic activity, exposure of MCF-7 cells to equol simultaneously with oestradiol was effective in reducing pS2 mRNA expression. This was not observed with daidzein. However, long-term exposure of MCF-7 cells to both daidzein and equol resulted in the downregulation of ER mRNA expression.
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PMID:Differential effects of dietary phyto-oestrogens daidzein and equol on human breast cancer MCF-7 cells. 961 86

Northern hybridization analyses of the oestrogen-inducible mRNAs pLIV1 and pS2 were compared with oestrogen receptor (ER) immunocytochemistry assessments in 40 untreated primary or early recurrent breast tumours. Significant associations were observed between pLIV1/ER (P < 0.03), pS2/ER (P < 0.001) and pLIV1/pS2 (P < 0.04) status. After disease recurrence, patients were treated with assessable courses of endocrine therapies. Positive pLIV1, pS2 and ER statuses in primary disease were consequently found to be predictive of endocrine responsiveness in the secondary lesions (P < 0.03, P < 0.02, P < 0.005 respectively). However, despite these associations, a number of pLIV1- and/or pS2-positive tumours failed to respond to therapy.
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PMID:Oestrogen-regulated genes in breast cancer: association of pLIV1 with response to endocrine therapy. 963 43

The histogenesis of phyllodes tumour (PT) and that of fibroadenoma (FA) of the breast appear to be closely related. FA is thought to be hormonally responsive, while the hormone-responsiveness of PT is uncertain. To gain insight into hormone-responsiveness of PT, we performed immunohistochemical analysis of oestrogen-regulated pS2 and androgen-regulated prostate-specific antigen (PSA) protein expression and also of oestrogen receptor (ER), progesterone receptor (PgR) and androgen receptor (AR) expression in paraffin sections obtained from 50 female PT patients. Paraffin sections taken from 50 female fibroadenoma (FA) patients were analysed for comparison. ER, PgR, pS2, AR and PSA expression were detected in 32%, 96%, 20%, 98% and 4.0% of PT sections and in 28%, 96%, 42%, 80% and 10% of FA sections, respectively. No correlations were detected among ER, PgR and pS2 expression or between AR and PSA expression in PT or FA sections. PgR expression was significantly associated with AR expression in PT (P<0.0001). The present investigations indicate that PT and FA have almost similar hormone receptor status. However, different positivities of pS2 expression suggest that oestrogen-responsiveness may differ between PT and FA. In addition, a wide-ranging co-expression of AR and PgR in PT sections suggests that these receptors may play an important part in the proliferation, although the functional significance of these receptors should be elucidated.
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PMID:Immunohistochemical study of hormone receptor and hormone-regulated protein expression in phyllodes tumour: comparison with fibroadenoma. 980 32

There is controversy concerning the prognosis of breast cancers arising in women carrying loss of function mutations in the breast cancer susceptibility genes BRCA1 and BRCA2. This study was carried out to assess the likely hormone dependence of this group of tumours in comparison with an age and grade matched group of control sporadic tumours. We used quantitative immunohistochemical analysis for the oestrogen receptor (ER), progesterone receptor (PgR), cyclin D1 and pS2 on sections of primary tumours and ductal carcinoma in situ (DCIS). Expression of PgR (P < 0.05) and cyclin D1 (P < 0.01) was low in the BRCA1- and BRCA2-associated cancers compared with sporadic cases. The low frequency of expression of ER (9/40), PgR (2/40) cyclin D1 (5/36) and pS2 (5/36) in the familial tumours indicates that the majority of such tumours will be oestrogen insensitive and unlikely to respond to hormonal manipulation even at the in situ stage in their evolution. The low level of PgR (2/40 cases) suggests that there may be some abnormality of transactivating function of the ER in these tumours.
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PMID:Predicted anti-oestrogen resistance in BRCA-associated familial breast cancers. 989 52

The trefoil peptide pS2 was discovered in a breast cancer cell line as a result of its oestrogen responsive character. The expression of pS2 in breast tumours in vivo is also likely to be an oestrogenic effect and as such, the presence of pS2 in oestrogen receptor positive breast cancer is evidence of an intact oestrogen response pathway and an indicator of putative hormone responsiveness. Consistent with this, clinical studies of breast cancer have revealed a correlation between pS2 expression and favourable tumour characteristics as well as response to endocrine therapy.
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PMID:Expression of the oestrogen responsive protein pS2 in human breast cancer. 1021 19

We compared the oestrogenic and anti-oestrogenic properties of the two well-known phyto-oestrogens, genistein and quercetin, on the oestrogen-sensitive breast cancer cell line MCF-7. Genistein exerted a biphasic effect on growth of MCF-7 cells, stimulating at low and inhibiting at high concentrations, whereas quercetin was only growth inhibitory. At doses which did not inhibit cell growth, respectively 5 and 1 microM, genistein and quercetin counteracted oestrogen- and transforming growth factor-alpha-promoted cell growth stimulation. Furthermore, genistein promoted transcription of the oestrogen-regulated genes pS2 and cathepsin-D, whereas quercetin interfered with the oestrogen-induced expression of the proteins. In in vitro binding experiments, genistein competed with oestradiol for binding to the oestrogen receptor (ER), but quercetin did not. Quercetin and genistein down-regulated cytoplasmic ER levels and promoted a tighter nuclear association of the ER, but only genistein was able to up-regulate progesterone receptor protein levels. In gel mobility assays, ER preincubation with oestradiol or with the two phyto-oestrogens led to the appearance of the same retarded band, excluding differences between the various complexes in binding to the consensus sequence. The data allowed us to conclude that quercetin acts like a pure anti-oestrogen, whereas genistein displays mixed agonist/antagonist properties, and to formulate a hypothesis on the possible mechanism of action of such phyto-oestrogens.
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PMID:The two phyto-oestrogens genistein and quercetin exert different effects on oestrogen receptor function. 1037 65

Although cytosolic expression of the protein pS2 (TFF1) is considered to be a marker of oestrogen receptor (OR) function, there exists some clinical data to suggest an inverse relationship of cytosolic pS2 to tumour proliferation. Although secreted from breast cancer cells, the relationship of pS2 secretion to tumour natural history has been little studied. The mechanisms and kinetics of pS2 release and its relation to tumour cell proliferation were studied in a human breast cancer cell line MCF-7 and verified in a preliminary clinical study. Stimulation by stripped serum or oestradiol resulted in parallel increases of proliferation and pS2 release in both time course and dose-response experiments. Direct pharmacological alterations of proliferation were followed by identical changes in pS2 release. The relationship between serum pS2 levels and tumour proliferative activity when analysed as a function of steroid status showed a slope of 0.56 in OR+ vs. 0.19 in OR- tumours. It is concluded that pS2 release from breast cancer cells is associated with their proliferation and measurement of serum pS2 levels might be a good predictor of tumour proliferative state and could permit noninvasive monitoring of this tumour parameter.
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PMID:Association of pS2 (TFF1) release with breast tumour proliferative rate: in vitro and in vivo studies. 1053 57


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