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

The study of several human estrogen receptor positive breast cancer cell lines has allowed characterization of a number of estrogen-induced proteins (e.g. progesterone receptor, cathepsin D, pS2 and fibulin-1 in ovarian cell lines). In primary tumours, these markers have different prognostic significance for predicting whether the tumour will be hormone responsive (e.g. pS2, estrogen and progesterone receptors) or will develop metastasis (e.g. cathepsin D). Studies of estrogen-regulated genes should also lead to new therapeutic approaches for hormone-resistant cancers. The role of estrogens as mitogens stimulating the growth of breast and ovarian cancer cell lines is well established. By contrast, their action on metastasis appears more ambiguous. Breast cancer cells without estrogen receptor (ER) are generally less differentiated and more aggressive than those containing functional ER. Moreover, the reexpression of ER by transfection in ER-negative cell lines inhibit their metastatic and invasive potential. These results suggest a protective role of ER in tumor progression. Studies of the underlying mechanisms of this effect may open new therapeutical strategies.
 ...
PMID:[Estrogen-induced genes in breast cancer, and their medical importance]. 1046

The cytosol values of estrogen-regulated proteins cathepsin D and pS2 were evaluated in 166 patients with breast diseases by a receiver-operating characteristic (ROC) curve analysis. Our aim was to compare their diagnostic accuracy and to define optimal cut-off levels for the cytosol values of these proteins in breast cancer (n = 133). The preoperative mean cytosol cathepsin D values in the breast cancer group were higher than in patients with benign breast disease (p < 0.001). The correlation coefficient (Pearson's r) between Cathepsin D and pS2 measurements was 0.286 (p < 0.001) in breast cancer patients. The ROC analysis indicated that the cathepsin D test was more sensitive than the pS2 test at all specificity levels, and the cathepsin D test reached considerably high sensitivity (86%) at the specificity level of 80%. According to present study, it would seem optimal to use the cut-off level of 33.0 pmol/mg for cathepsin D analysis and the level of 31.0 ng/mg for pS2 in breast cancer. In conclusion, the results of ROC curve analysis suggest that the cathepsin D test has advantage over pS2 because of its higher sensitivity in breast cancer.
 ...
PMID:Receiver-operating characteristic (ROC) curve analysis of cathepsin D and pS2 in breast disease; results from a prospective study. 1062 36

Anti-oestrogen therapy is being used in an attempt to prevent breast cancer but no intermediate end points of the effect of tamoxifen on the normal breast are available. Therefore, the purpose of this study was to develop a physiological measure of oestrogen action on the breast. We measured oestrogen-stimulated and -inhibited proteins in breast secretions from women on and off anti-oestrogen therapy. Two oestrogen-stimulated proteins (pS2 and cathepsin D) and oestrogen-inhibited proteins (CP15, gross cystic disease fluid protein 15; Apo,: apolipoprotein D) were measured. Premenopausal women had significantly higher pS2 and cathepsin D in association with lower Apo D and CP15 secretion levels compared to post-menopausal women. Sequential nipple aspirates from women treated with the luteinizing hormone releasing hormone agonist goserelin (n = 9), tamoxifen (n = 9) and hormone replacement therapy (HRT) (n = 26) were measured. Following treatment with goserelin, median nipple secretion levels of pS2 fell (P < 0.02) and Apo D and CP15 rose significantly (P < 0.03 and P < 0.05 respectively). Similar changes were seen on tamoxifen therapy but not in untreated control women. Treatment with HRT resulted in a rise of pS2 (P < 0.001) and a fall in Apo D (P < 0.05). Measurement of pS2 and Apo D in nipple aspirates may prove useful intermediate end point of breast responsiveness to anti-oestrogens.
 ...
PMID:Hormonally-regulated proteins in breast secretions are markers of target organ sensitivity. 1064 88

Our aim was to compare the occurrence and prognostic significance over 14-20 years of immunocytochemically detected S100A4 and other tumour variables in primary tumours from 349 patients with operable breast cancer. For a cut-off of 1% staining of the malignant cells, the antibody to S100A4 stains positively 56% of the carcinomas. There was a significant association of staining for S100A4 with tumours fixed to the chest wall, staining for c-erbB-2, c-erbB-3, pS2, cathepsin D and, inversely, at borderline levels with staining for estrogen receptor. Using Wilcoxon statistics in univariate analyses, staining for S100A4, nodal status, tumour class, histological grade and staining for c-erbB-2, p53 were associated negatively and staining for estrogen receptor, progesterone receptor were associated positively with patient survival times. The survival times of patients with S100A4-negative carcinomas with or without one of the other tumour variables showed no significant differences, whilst those of patients with S100A4-positive carcinomas showed significant differences in a negative or a positive way. Multivariate regression analysis for 137 patients showed that staining for S100A4 is most highly correlated with patient deaths, but involved lymph nodes, fixed tumours, high histological grade and staining for progesterone receptor were also significant independent prognostic variables. Our results suggest that in this set of patients, the tumour variable most tightly correlated with patient death is S100A4.
 ...
PMID:Comparison of the metastasis-inducing protein S100A4 (p9ka) with other prognostic markers in human breast cancer. 1075

A human tamoxifen-resistant mammary carcinoma, MaCa 3366/TAM, originating from a sensitive parental xenograft 3366 was successfully established by treatment of tumour-bearing nude mice with 1-50 mg kg(-1) tamoxifen for 3 years during routine passaging. Both tumours did not differ significantly in OR- and PR-positivity, however, when compared with the sensitive tumour line, the mean OR content of the TAM-resistant subline is slightly lower. An OR-upregulation following withdrawal of oestradiol treatment was observed in the parental tumours but not in the resistant xenografts. Following long-term treatment with tamoxifen, the histological pattern of the breast carcinoma changed. The more differentiated structures being apparent after treatment with 17beta-oestradiol in the original 3366 tumour were not induced in the resistant line. Tamoxifen failed to induce a tumour growth inhibition in comparison to the tamoxifen-sensitive line. The pure anti-oestrogen, ICI 182 780, revealed cross-resistance. Sequence analysis of the hormone-binding domain of the OR of both lines showed no differences, suggesting that either mutations in other regions of the OR are involved in the TAM-resistance phenotype or that mechanisms outside of this protein induced this phenotype. Oestrogen and anti-oestrogen regulate pS2 and cathepsin D expression in 3366 tumours as in the human breast cancer cell line MCF-7. The resistant 3366/TAM tumours have lost this regulation. The established breast cancer xenografts 3366 and 3366/TAM offer the possibility of investigating mechanisms of anti-oestrogen resistance in an in vivo situation. They can be used to test novel approaches to prevent, or to overcome, this resistance in a clinically related manner.
 ...
PMID:Development and characterization of a tamoxifen-resistant breast carcinoma xenograft. 1083

Chromatin restricts the accessibility of DNA to regulatory factors; its remodeling over the regulatory regions contributes to the control of gene expression. An increasing number of evidence links defects in chromatin remodeling machinery and cancer. Our aim is to elucidate the role of chromatin structure in the control of the expression of hormone-induced genes in breast cell lines estrogen-dependent or -independent for growth. Mammary tumor growth is controlled by steroid hormones via their nuclear receptor and by growth factors via tyrosine kinase receptors. 50 % of these tumors elude to hormonal control. This limits the anti-estrogen therapy. As a model, we have analyzed in several cell lines the chromatin organization of the regulatory regions of two genes, pS2 that is associated with a good prognostic, and cathepsin D (catD) that is a bad prognostic marker. The expression of the two genes is estrogen-regulated in estrogen-dependent cell line MCF7. In contrast in the hormone-independent cell line MDA MB 231, pS2 is not expressed and catD is constitutively expressed. Within the regulatory regions of pS2 gene, we have localized two regions that undergo a hormone-dependent change in chromatin structure in MCF7 cells but not in MDA MB 231. The lack of chromatin remodeling in MDA MB 231 cells is not due to the absence of expression of the estrogen receptor in the cell line. The expression of pS2 gene can be correlated with chromatin remodeling over the regulatory regions of pS2 gene. In contrast catD regulatory regions did not display hormone-dependent changes in chromatin structure, suggesting that hormone regulation takes place within regions with a constitutively open chromatin structure.
 ...
PMID:[Chromatin remodeling in estrogen-dependent and independent human breast cancer cell lines]. 1089 64

In order to search for novel estrogen-responsive genes, we performed serial analysis of gene expression (SAGE) for estrogen-treated MCF-7 human breast cancer cells. SAGE analysis of 31,000 and 30,856 tags from non-treated and 17 beta-estradiol (E2)-treated cells for 24 h, respectively, facilitated the identification of 15,037 different transcripts. Comparison of these two SAGE libraries indicated a remarkable similarity in expression profiles. Among the identified transcripts, four genes were found to be markedly increased for E2-treated cells compared with control cells. Three of the transcripts were cathepsin D, pS2 and high mobility group 1 protein, which have been described as estrogen-inducible genes. The fourth gene was WISP-2 (Wnt-1 inducible signaling pathway protein 2) which has recently been reported as an up-regulated gene in the mammary epithelial cell line C57 MG transformed by the Wnt-1 oncogene. The increase in WISP-2 mRNA was completely prevented by co-incubation with a pure anti-estrogen ICI 182,780, but not by coincubation with cycloheximide, indicating that WISP-2 is directly regulated by the estrogen receptor. The WISP-2 gene was also induced by treating with environmental estrogens, such as bisphenol-A or nonylphenol. This study represents the first comprehensive gene expression analysis of estrogen-treated human breast cancer cells.
 ...
PMID:WISP-2 as a novel estrogen-responsive gene in human breast cancer cells. 1094 50

Chromatin restricts the accessibility of DNA to regulatory factors; its remodelling over the regulatory regions contributes to the control of gene expression. An increasing number of evidence links defects in chromatin remodelling machinery and cancer. Our aim is to elucidate the role of chromatin structure in the control of the expression of hormone-induced genes in breast cell lines oestrogen-dependent or -independent for growth. Mammary tumour growth is controlled by steroid hormones via their nuclear receptor and by growth factors via tyrosine kinase receptors. 50% of these tumours elude to hormonal control. This limits the anti-oestrogen therapy. As a model, we have analysed in several cell lines the chromatin organisation of the regulatory regions of two genes, pS2 that is associated with a good prognostic, and cathepsin D (catD) that is a bad prognostic marker. The expression of the two genes is oestrogen-regulated in oestrogen-dependent cell line MCF7. In contrast in the hormone-independent cell line MDA MB 231, pS2 is not expressed and catD is constitutively expressed. Within the regulatory regions of pS2 gene, we have localised two regions that undergo a hormone-dependent change in chromatin structure in MCF7 cells but not in MDA MB 231 and that can be correlated with gene expression. In contrast catD regulatory regions did not display hormone-dependent changes in chromatin structure, suggesting that hormone regulation takes place within regions with a constitutively open chromatin structure.
 ...
PMID:Chromatin remodeling in hormone-dependent and -independent breast cancer cell lines. 1095 22

In order to investigate the possible hormone-dependence of CD44v6 in human breast cancer, we assayed the concentrations of this isoform in the membrane fraction of 168 invasive ductal carcinomas (IDC) and in 26 normal breast tissue samples, 18 fibradenomas (FAD), 3 fibrocystic disease specimens (FD), 7 mucinous carcinomas and 4 medullary carcinomas using the ELISA method. The results were compared with those of the estrogen (ER) and progesterone (PR) receptors, pS2, tissue type plasminogen activator (t-PA), cathepsin D, epidermal growth factor receptor (EGFR) and c-erbB2/neu oncoprotein concentrations. Menopausal status, size of the tumor in the cases of cancers, axillary lymph node involvement, histologic grade, ploidy, cellular synthesis phase, multifocality and multicentricity were also considered as variables. The cut-off value for CD44v6-positivity was set at 5 ng/mg prt. membrane protein content. 64/138 (38.1%) infiltrating ductal carcinomas scored positive. This was significantly higher than for the normal breast tissue (0/26; p: 0.0001), similar to that seen in the FAD (3/18), fibrocystic disease (0/3), infiltrating mucinous carcinomas (4/7) and lobular (3/15) and significantly lower than for the infiltrating medullary carcinomas (4/4; p: 0.027). There were no significant differences with the other groups of tissues studied. Furthermore, CD44v6-positive IDC showed significantly higher concentrations of ER, PR and cathepsin D and lower (p: 0.051) concentrations of EGFR when compared to their CD44v6-negative counterparts. The significant coexpression of ER, PR and cathepsin D seems to indicate a possible role for hormonal regulation of CD44v6 expression while the role of pS2 and t-PA, estrogen related proteins, was very reduced.
 ...
PMID:[Expression of the adhesion molecule CD44v6 in infiltrating ductal carcinomas of the breast is associated with hormone dependence. Our experience with 168 cases]. 1106 11

The BRCA1 gene was previously found to inhibit the transcriptional activity of the estrogen receptor [ER-alpha] in human breast and prostate cancer cell lines. In this study, we found that breast cancer-associated mutations of BRCA1 abolish or reduce its ability to inhibit ER-alpha activity and that domains within the amino- and carboxyl-termini of the BRCA1 protein are required for the inhibition. BRCA1 inhibition of ER-alpha activity was demonstrated under conditions in which a BRCA1 transgene was transiently or stably over-expressed in cell lines with endogenous wild-type BRCA1 and in a breast cancer cell line that lacks endogenous functional BRCA1 (HCC1937). In addition, BRCA1 blocked the expression of two endogenous estrogen-regulated gene products in human breast cancer cells: pS2 and cathepsin D. The BRCA1 protein was found to associate with ER-alpha in vivo and to bind to ER-alpha in vitro, by an estrogen-independent interaction that mapped to the amino-terminal region of BRCA1 (ca. amino acid 1-300) and the conserved carboxyl-terminal activation function [AF-2] domain of ER-alpha. Furthermore, several truncated BRCA1 proteins containing the amino-terminal ER-alpha binding region blocked the ability of the full-length BRCA1 protein to inhibit ER-alpha activity. Our findings suggest that the amino-terminus of BRCA1 interacts with ER-alpha, while the carboxyl-terminus of BRCA1 may function as a transcriptional repression domain. Oncogene (2001) 20, 77 - 87.
 ...
PMID:Role of direct interaction in BRCA1 inhibition of estrogen receptor activity. 1124 6


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>