UNIPROT:P04155 - FACTA Search

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Query: UNIPROT:P04155 (pS2)
1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

[3H]Tamoxifen Aziridine ([3H]TAZ) is a derivative of the antiestrogen tamoxifen that covalently labels the Estrogen Receptor (ER), and perhaps other uncharacterized proteins. In a previous article we described that [3H]TAZ binds to a cytosolic protein from human uterine tissues that shares some, but not all, the ER properties. Here we have extended these studies to [3H]TAZ binding to cytosol proteins from human breast cancer specimens, and studied its quantitative association with other molecular markers and clinico-pathological variables. Cytosols were obtained in hypotonic buffer containing 20 mM molybdate and protease inhibitors, incubated with [3H]TAZ, and subjected to Sucrose Gradient Analysis (SGA). A [3H]TAZ labeled peak that consistently migrated with the 4S fractions was found in most of the assayed cytosols (range of 0 to 1278 fmol/ mg p.). The 4S peak of [3H]TAZ was partially inhibited by both estrogens and antiestrogens. When [3H]E2 was used instead of [3H]TAZ, only an 8S peak was detected. [3H]TAZ was covalently bound to a protein with an apparent MW of 65 kDa, as determined by SDS-PAGE and fluorography. The mean of [3H]TAZ binding was significantly higher in the subgroups of samples classified as ER-, PR-, pS2- or cathepsin D-, than in the respective positive subgroups (P < 0.01 in all the cases). [3H]TAZ binding was not associated with clinico-pathological variables, except that its mean was significantly larger in tumors larger than 5 cm than in smaller tumors. These results, and those previously reported, suggest that: 1) [3H]TAZ labels a cytosolic protein present in human breast cancers and uterine tissues that does not share all the ER properties, and 2) the [3H]TAZ binding by breast cancer cytosols is negatively associated with markers of estrogenic dependency, and its quantification may provide valuable information on antiestrogen responsiveness of a given tumor.
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PMID:Tamoxifen aziridine binding to cytosolic proteins from human breast specimens is negatively associated with estrogen receptors, progesterone receptors, pS2, and cathepsin-D. 982 20

In many cancer cell lines, including breast, prostate, lung, brain, head and neck, retina, and the gastrointestinal tract, opioids decrease cell proliferation in a dose-dependent and reversible manner. Opioid and/or other neuropeptide receptors mediate this decrease. We report that only the steroid-hormone-sensitive cell lines MCF7 and T47D respond to opioid growth inhibition in a dose-dependent manner. Therefore, an interaction of the opioid and steroid receptor system might exist, as is the case with insulin. To investigate this interaction, we have assayed two estrogen-inducible proteins (pS2 and the lysosomal enzyme cathepsin D) in MCF7 and T47D cells. When cells were grown in the presence of FBS (in which case a minimal quantity of estrogens and/or opioids is provided by the serum), we observed either no effect of etorphine or ethylketocyclazocine (EKC) or an increase of secretion and/or production of pS2 and cathepsin D. However, when cells were cultured in charcoal-stripped serum and in the absence of phenol red, the effect of the two opioids is different: EKC decreased the production and/or secretion of pS2 and cathepsin D, whereas etorphine increased their synthesis and/or secretion. The differential effect of the two general opioids was attributed to their different receptor selectivity. Furthermore, the variations of the ratio of secreted/produced protein and the use of cycloheximide indicate that opioids selectively modify the regulatory pathway of each protein discretely. In conclusion, through the interaction with opioid and perhaps other membrane-receptor sites, opioid agonists modify in a dose-dependent manner the production and the secretion of two estrogen-regulated proteins. Opioids may therefore disturb hormonal signals mediated by the estrogen receptors. Hence, these chemicals may have potential endocrine disrupting activities.
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PMID:Modulation of the estrogen-regulated proteins cathepsin D and pS2 by opioid agonists in hormone-sensitive breast cancer cell lines (MCF7 and T47D): evidence for an interaction between the two systems. 983 Oct 78

We have compared the DNase I hypersensitivity of the regulatory region of two estrogen-regulated genes, pS2 and cathepsin D in hormone-dependent and -independent breast carcinoma cell lines. This strategy allowed the identification of two important control regions, one in pS2 and the other in cathepsin D genes. In the hormone-dependent MCF7 cell line, within the pS2 gene 5'-flanking region, we detected two major DNase I hypersensitive sites, induced by estrogens and/or IGFI: pS2-HS1, located in the proximal promoter and pS2-HS4, located -10.5 Kb from the CAP site, within a region that has not been cloned. The presence of these two DNase I hypersensitive sites correlates with pS2 expression. Interestingly in MCF7 cells, estrogens and IGFI induced indistinguishable chromatin structural changes over the pS2 regulatory region, suggesting that the two transduction-pathways converge to a unique chromatin target. In two cell lines that do not express pS2, MDA MB 231, a hormone-independent cell line that lacks the estrogen receptor alpha, and HE5, a cell line derived from MDA MB 231 by transfection that expresses estrogen receptor alpha, there was only one hormone-independent DNase I hypersensitive site. This site, pS2-HS2, was located immediately upstream of pS2-HS1. In MCF7 cells, two major DNase I hypersensitive sites were present in the 5'-flanking sequences of the cathepsin D gene, which is regulated by estrogens in these cells. These sites, catD-HS2 and catD-HS3, located at positions -2.3 Kb and -3.45 Kb, respectively, were both hormone-independent. A much weaker site, catD-HS1, covered the proximal promoter. In MDA MB 231 cells, that express cathepsin D constitutively, we detected an additional strong hormone-independent DNase I hypersensitive site, catD-HS4, located at position -4.3 Kb. This region might control the constitutive over-expression of cathepsin D in hormone-independent breast cancer cells. All together, these data demonstrate that a local reorganization of the chromatin structure over pS2 and cathepsin D promoters accompanies the establishment of the hormone-independent phenotype of the cells.
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PMID:Chromatin structure of the regulatory regions of pS2 and cathepsin D genes in hormone-dependent and -independent breast cancer cell lines. 992 10

Estrogen receptors are derived from two different gene products referred to as estrogen receptor-alpha (ER-alpha) and ER-beta. Both receptors bind to the consensus estrogen response element (ERE) present in the vitellogenin gene, but their binding to hormone response elements present in other estrogen responsive genes has not been reported yet. Using in vitro expressed human receptors, we now show that ER-beta binds to a panel of six endogenous hormone response elements (vitellogenin, c-fos, c-jun, pS2, cathepsin D, and choline acetyltransferase) already known to bind ER-alpha and confer estrogen inducibility to reporter constructs. Binding of ER-alpha and ER-beta occurred at similar DNA concentrations for some EREs, but different DNA concentrations were required to form complexes of the two receptors with other elements. These results illustrate for the first time by direct receptor-DNA binding studies that both ER-alpha and ER-beta bind to a number of EREs present in endogenous hormone regulated genes, and further suggest that the two forms of the receptor display different patterns of affinities for naturally occurring hormone response elements.
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PMID:Interaction of human estrogen receptors alpha and beta with the same naturally occurring estrogen response elements. 1003 43

Many studies have addressed the clinical value of pS2 as a marker of hormone responsiveness and of cathepsin D (Cath D) as a prognostic factor in breast cancer. Because pS2 and Cath D are both oestrogen induced in human breast cancer cell lines, we studied the influence of the menstrual cycle phase and menopausal status at the time of surgery on the levels of these proteins in breast cancer. A population of 1750 patients with breast cancer, including 339 women in menstrual cycle, was analysed. Tumoral Cath D and pS2 were measured by radioimmunoassay. Serum oestradiol (E2), progesterone (Pg), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels at the day of surgery were used to define the hormonal phase in premenopausal women. There was a trend towards a higher mean pS2 level in the follicular phase compared with the luteal phase (17 ng mg(-1) and 11 ng mg(-1) respectively, P = 0.09). Mean pS2 was lower in menopausal patients than in women with cycle (8 ng mg(-1) and 14 ng mg(-1) respectively, P = 0.0001). No differences in mean Cath D level were observed between the different phases of the menstrual cycle, or between pre- and post-menopausal women. In the overall population, pS2 was slightly positively associated with E2 and Pg levels and negatively associated with FSH and LH, probably reflecting the link between pS2 and menopausal status. In premenopausal women, no association was found between pS2 and E2, Pg, FSH or LH levels. There were no correlations between Cath D level and circulating hormone levels in the overall population. However, in the subgroup of premenopausal women with ER-positive (ER+) tumours, E2 was slightly associated with both pS2 and Cath D, consistent with oestrogen induction of these proteins in ER+ breast cancer cell lines. There are changes in pS2 level in breast cancer throughout the menstrual cycle and menopause. This suggests that the choice of the pS2 cut-off level should take the hormonal status at the time of surgery into account. In contrast, the level of Cath D is unrelated to the menstrual cycle and menopausal status.
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PMID:Time at surgery during menstrual cycle and menopause affects pS2 but not cathepsin D levels in breast cancer. 1007 Aug 89

The human breast epithelial cell line, MCF-10A, derived from tissue from a woman undergoing a cutaneous mastectomy for fibrocystic breast disease, is negative for estrogen receptor expression, has undergone minimal genetic changes, retains many of the characteristics of normal breast epithelium and fails to exhibit growth in nude mice. When transfected with a functional copy of the estrogen receptor, both ER and MDM2 expression are negatively regulated by the presence of increasing concentrations of estradiol, as previously reported. We obtained the MCF-10A cell line from the American Type Culture Collection and confirmed that it was negative for ER expression. After approximately 20 passages under differing growth conditions, one subline was determined to be positive for ER expression. Growth of this ER-positive subline in phenol red-free media supplemented with charcoal-dextran stripped serum in the presence of nanomolar concentrations of estradiol failed to modulate ER and MDM2 expression, and induced expression of both pS2 and cathepsin D. Simultaneously with these observations, we observed that this subline, unlike the parent MCF-10A line, overexpressed P53 protein with a nuclear localization. Intermediate levels of the P53-inducible protein p21 WAF1/Cip1 were also detected in the ER-positive subline whereas levels of this protein in the parent subline were barely detectable, as measured by immunohistochemical methods. We conclude from these studies that ER expression and P53 alteration may constitute early steps in progression of malignant potential for breast cancer development.
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PMID:Spontaneous conversion to estrogen receptor expression by the human breast epithelial cell line, MCF-10A. 1020 82

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.
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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.
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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.
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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.
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PMID:Comparison of the metastasis-inducing protein S100A4 (p9ka) with other prognostic markers in human breast cancer. 1075

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