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)

Apolipoprotein D (apo D) is a glycoprotein involved in the human plasma lipid transport system and present at large amounts in cyst fluid from women with gross cystic disease of the breast. Apo D expression in breast carcinomas was examined by immunoperoxidase staining of a series of 163 tumors. A total of 60 (36.8%) tumors were negative for apo D immunostaining, 28 (17.2%) carcinomas were weakly positive, 33 (20.2%) were moderately stained, whereas the remaining 42 (25.8%) tumors were strongly stained with the specific antibodies. No significant correlation was found between apo D content and tumor size, lymph node involvement, or biochemical parameters such as estrogen receptors, cathepsin D, or pS2 protein. However, the finding of a significant association between apo D and menopausal status of patients or differentiation grade of tumors, with apo D values being lower in tumors from premenopausal women or in poorly differentiated carcinomas, suggested a potential value of this glycoprotein as a prognostic factor in breast cancer. Preliminary analysis of relapse-free survival and overall survival in a subgroup of 152 women with a mean follow-up of 42 months confirmed that low apo D values were significantly associated to a shorter relapse-free survival and poorer survival. According to these data, we propose that apo D in combination with other well-established prognostic factors may contribute to more accurately identify subgroups of breast cancer patients with low or high risk for relapse and death.
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PMID:Expression and prognostic significance of apolipoprotein D in breast cancer. 831 Nov 15

The influence of structural alterations to the estradiol-17 beta (E2) molecule on the induction of pS2 and Cathepsin D (Cath D) mRNAs has been examined by Northern analysis of RNA extracted from MCF-7 cells. Exposure of cultures to estratriene did not affect the level of expression of these estrogen-responsive genes. Addition of one hydroxyl group to estratriene at either of the hydroxylated positions of E2 (3-phenolic or 17 beta) yielded monohydroxyestrogens which stimulated the synthesis of Cath D and pS2 mRNAs to a level comparable to that induced by 10(-10) M E2 and displayed a decrease in activity at the higher concentrations (10(-8) - 10(-7) M) similar to that of the parent estrogen. Both of these genes were induced maximally by estrogens with D-ring alterations. Movement of the phenolic hydroxyl group of E2 to other positions on the A-ring yielded ligands which were highly discriminatory in the induction of these messages. 1-Hydroxyestratrien-17 beta-ol was capable of stimulating maximal synthesis of both pS2 and Cath D mRNAs when added to cultures of MCF-7 cells at a concentration of 10(-8) M. Placement of the phenolic hydroxyl at position 4 greatly diminished the induction of these two estrogen-responsive genes. On the other hand, positioning the A-ring hydroxyl group on carbon 2 yielded a ligand which brought about the induction of one gene (pS2) but was marginally effective in the induction of Cath D mRNA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential induction of pS2 and cathepsin D mRNAs by structurally altered estrogens. 833 30

Zn-alpha 2-glycoprotein (Zn-alpha 2-gp), a protein present at high levels in breast cyst fluid, has been measured in 104 breast tumour cytosols by using an immunoenzymatic assay. Concentrations of Zn-alpha 2-gp ranged from 0 to 23.5 micrograms/mg of total soluble protein, with an average value of 2.4 micrograms/mg. There was no significant correlation between Zn-alpha 2-gp and menopausal status, tumour size or lymph node involvement, or between this protein and biochemical parameters such as oestrogen receptor, cathepsin D or pS2 levels. However, there was a significant association between Zn-alpha 2-gp and histological grade of tumours, with higher Zn-alpha 2-gp levels in well-differentiated tumours (mean 4.6 micrograms/mg) than in moderately (1.8 micrograms/mg) or poorly (0.9 micrograms/mg) differentiated tumours. On the basis of these results, we propose that Zn-alpha 2-gp may be considered as a biochemical marker of differentiation in breast cancer.
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PMID:Zn-alpha 2-glycoprotein levels in breast cancer cytosols and correlation with clinical, histological and biochemical parameters. 834 63

The oestrogen induced pS2 protein was measured in the cytosol of 446 breast cancer samples by an immunoradiometric assay. The relationships between pS2 and several clinical and biological parameters were evaluated. pS2 was not correlated to age, pT and nodal status, while it was higher in pre- than in peri- and post-menopausal women. A statistically significant positive association was found between pS2 and ER, PgR and cathepsin D. However, the frequency of pS2 negative values in ER+ (25.6%), PgR+ (21.7%) and cathepsin D-(19.0%) cases suggests that pS2 provides information independent of the above parameters in a fairly high percentage of patients. The prognostic role of pS2 was evaluated in 267 cases (follow up time 24-102 months). pS2+ showed longer RFS (P = 0.016) and OS (P = 0.004) than pS2-. pS2+ cases were significantly associated with a better prognosis in N+ but not in N- cases. Multivariate analysis showed that pS2 is an independent prognostic factor being the second most effective indicator for OS after nodal status and the third for RFS after nodal status and cathepsin D. From the present findings, we conclude that pS2 probably provides additional biological information to steroid receptor status and cathepsin D in patients with primary breast cancer.
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PMID:PS2 in breast cancer--alternative or complementary tool to steroid receptor status? Evaluation of 446 cases. 834 94

A novel oestrogen-responsive breast-tumour cell line, EFF-3, has been established from a pleural exudate of a patient with metastatic breast cancer. The cells show morphological and immunohistochemical features consistent with their origin from a metastatic breast carcinoma. The cells aggregate and form sheets in culture, and electron microscopy confirms the presence of cell-surface microvilli and intercellular tight junctions. The epithelial origin of EFF-3 cells was confirmed by their expression of low-molecular-weight cytokeratins and carcinoembryonic antigen. The karyotype of the cells is markedly abnormal and there are large numbers of structurally abnormal chromosomes. EFF-3 cells express oestrogen receptor, oestrogen-receptor mRNA, their growth is oestrogen-responsive, and specific genes are regulated by oestrogens. The pNR-2/pS2 and pNR-25 oestrogen-regulated mRNAs are induced 15- and 13-fold respectively by oestrogen, whereas the oestrogen-receptor and cathepsin D mRNAs are not regulated. This pattern of regulation differs from that reported previously for other cell lines. The EFF-3 cell line should be useful for studying the mechanisms involved in oestrogen-stimulated proliferation and the factors determining the regulation of specific genes by oestrogens.
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PMID:Isolation and characterization of an oestrogen-responsive breast-cancer cell line, EFF-3. 842 92

Women who have breast cysts with intracystic Na+/K+ < 3 may have a higher risk of developing breast cancer than women who have breast cysts with intracystic Na+/K+ > 3. In this study wide-ranging intracystic concentrations of cathepsin D and pS2 (oestrogen inducible proteins/polypeptides) as well as oestradiol were found. The concentrations of cathepsin D and oestradiol were significantly higher in the low electrolyte ratio cyst group than in the high electrolyte ratio cyst group. No significant difference was found between pS2 concentrations in the two groups. The significantly higher intracystic concentrations of cathepsin D, a mitogenic lysosomal endopeptidase and oestradiol in the low electrolyte ratio group may partly provide an explanation for the higher risk of breast cancer which has been observed in this group of women.
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PMID:Relationships between oestrogen-inducible proteins, oestradiol and electrolyte ratio in breast cyst fluid. 848 90

The study of several human breast cancer cell lines containing oestrogen receptors has allowed characterization of a number of oestrogen-induced proteins (e.g. progesterone receptor, cathepsin D, pS2, Hsp27, c-Myc). In primary tumours these markers have different prognostic significance for predicting whether the tumour will be hormone responsive (e.g. pS2, progesterone receptor) and whether it will metastasize (e.g. cathepsin D). The mechanism of regulation of gene expression by oestrogens and anti-oestrogens in breast cancer is complex and varies according to the nature of both the gene and the cell in which it is transcribed. Our laboratory has identified the sequences mediating oestrogen activity in the proximal region of cathepsin D, including a non-consensus oestrogen-responsive element located at -260 which acts in synergy with other regulatory elements. In addition to the classical effect of oestrogen receptor in stimulating transcription of genes controlled by the oestrogen-responsive element, we found that estrogen receptor is able to modulate transcription of AP-1-responsive genes without interacting directly with DNA. Cross-talk between oestrogen receptor and members of the Fos/Jun family via protein-protein interactions may explain how anti-oestrogens inhibit the mitogenic effect of growth factors in the apparent absence of oestrogens and why tamoxifen is able to stimulate cathepsin D gene expression and induce apoptosis in certain oestrogen receptor-positive breast cancer cells. The nature and degree of this cross-talk appears to vary according to the gene, the cell type and the type of oestrogen receptor ligand involved. Studies of oestrogen-regulated genes are not only useful for classifying breast cancers according to their ability to metastasize and respond to therapies, but also should lead to new therapeutic approaches for hormone-dependent and hormone-resistant cancers.
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PMID:Oestrogen- and anti-oestrogen-regulated genes in human breast cancer. 858 2

Tamoxifen, although widely used in the treatment of estrogen-dependent tumors, is a partial estrogen agonist producing undesirable effects in breast cancer patients. ICI 182,780 a steroidal antiestrogen displays pure antagonist activity which is due to its ability to prevent dimerization of the estrogen receptor (ER). Our previous studies have shown that 1,1-dichloro-cis-2,3-diaryl cyclopropane (Analog II), a diarylcyclopropyl compound is devoid of estrogenic activity, has a weak binding affinity for the estrogen receptor in the mouse uterine tissue and inhibits the growth of breast cancer cells in culture. These findings suggest that Analog II may not inhibit tumor cell growth at the cellular level by an ER-mediated mechanism of action. Since these three antiestrogens appear to have different mechanisms of antiestrogenic activity, the purpose of this study was to compare the influence of the three antiestrogens on estradiol-induced expression of pS2 and cathepsin D (cath-D). These genes are known to be primarily under the influence of estrogen in ER positive MCF-7 human breast cancer cells. The results of this study demonstrate different mechanisms of regulation of the cath-D and pS2 genes by antiestrogens in MCF-7 cells. This study indicates that ICI 182,780 is a pure antagonist at the levels of gene regulation and cell proliferation. The relative order of inhibitory action was found to be ICI 182,780 > tamoxifen > Analog II.
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PMID:The influence of antiestrogens on pS2 and cathepsin D mRNA induction in MCF-7 breast cancer cells. 868 38

There has been increasing evidence which suggests that abnormal expression of the estrogen receptor (ER) protein in nonmalignant breast tissue may be important in the carcinogenic process. To examine the effects of ER expression in immortalized nonmalignant mammary epithelial cells, an expression vector containing human ER cDNA was transfected into the ER negative human breast cells, MCF10A. Characterization of a clone stably expressing ER, 139B6, provided evidence for the regulated synthesis of a functional ER capable of binding estradiol-17 beta (E2) and undergoing processing. Expression of the ER gene did not enable E2 to stimulate endogenous genes [progesterone receptor (PgR), pS2, cathepsin D and TGF alpha] which normally respond to estrogens in breast cancer cells. The ER in 139B6 cells was, however, capable of inducing expression of an ERE-regulated reporter gene, indicating its ability to interact with transcriptional machinery. Furthermore, cultures in log growth displayed a slight increase in doubling time in the presence of E2. These results indicate that ER expression alone is not sufficient to induce a transformed phenotype. Thus, the 139B6 cell line should provide a new model for determining what additional changes lead to increased growth potential in response to E2 and for exploring how E2 itself may help bring about changes leading to progression of preneoplastic breast epithelial cells.
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PMID:Characterization of the estrogen receptor transfected MCF10A breast cell line 139B6. 882 37

A series of 30 cases of male breast cancer in the North-East of Scotland is reviewed. The aims of the study were to document clinico-pathological and immunocytochemical features (available for 25) of these patients and to establish which factors could predict prognosis. Tumours were studied for the expression of oestrogen receptors (ERs), the oestrogen-dependent proteins pS2 and cathepsin D, the oncoprotein products of c-erb-B2 and the p53 tumour-suppressor-gene derived protein. Clinico-pathological features documented were in agreement with those reported by other authors. The overall 5-year survival was 53%. Tumour grade and lymph-node status influenced prognosis. In this series, 64% of the tumours expressed ERs, 50% pS2, 46% cathepsin D, 42% the c-erb-B2 transmembrane oncoprotein and 54% p53. In contrast to female breast cancer, the presence of either substantial amounts of ERs or the oestrogen-dependent protein pS2 correlated with poorer prognosis in males. This correlation has not previously been documented.
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PMID:Male breast cancer: clinico-pathological features, immunocytochemical characteristics and prognosis. 884 66


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