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)

Some node-negative breast cancer patients, with initially good prognosis, relapse from their cancer and are poorly identified. In the present study, based on prospective data of 197 tumors, we measured cathepsin D (cath D, n=197), pS2 protein (n=125), c-erbB-2 oncoprotein (n=100) and epidermal growth factor receptor (EGF-R, n=99) to better define the risk of relapse of node-negative patients in comparison with that defined by the clinical and histological factors. The median follow-up in surviving patients was 75 months. Univariate analysis indicated that patients with histological grade III tumors (the Scarff, Bloom and Richardson classification) had a much poorer prognosis than those with histological grade I or II tumors (P=0.0027 for relapse-free survival and P=0.0156 for overall survival). When the population of node-negative patients was divided by tertiles, high cath D levels showed a significant association with an early relapse (P=0.0316). Using cut-off values, patients with high cath D (> or =25 pmol/mg protein) or c-erbB-2 oncoprotein (> or =4 Human Neu Unit/microg protein) levels, had a significant worse relapse-free survival (P=0.0147 and 0.0417, respectively). No prognostic information was supported by pS2 protein or EGF-R measurements. In multivariate analysis, histological grade, cath D and c-erbB-2 oncoprotein remained independent predictors of recurrence (P=0.005, 0.0361 and 0.0321, respectively). By combining low levels of cath D and c-erbB-2 oncoprotein in histological grade I or II tumors, we identified a subgroup of patients with a 100% relapse-free survival probability at 6 years of follow-up. Moreover, the subgroup of patients with histological grade I or II tumors and high values of both cath D and c-erbB-2 oncoprotein showed a prognosis as poor as the subgroup defined by histological grade III alone, respectively 66% and 70% relapse-free survival at 6 years of follow-up. In conclusion, the combination of conventional prognostic factor (histological grade) and biochemical factors (cath D and c-erbB-2 oncoprotein) enabled us to identify, in this preliminary study, a subgroup of patients having an increased risk of relapse in a group (node-negative patients with low histological grade tumors) considered as good prognosis.
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PMID:Prognostic impact of cathepsin D and c-erbB-2 oncoprotein in a subgroup of node-negative breast cancer patients with low histological grade tumors. 1125 Nov 76

In order to study the association of histological grade (HG) with specific clinical and biological parameters which may influence the clinical behavior of infiltrating ductal carcinomas of the breast (IDC), we analyzed in 229 tissue samples the cytosolic concentrations of estrogen receptor (ER), progesterone receptor (PR), pS2, cathepsin D, hyaluronic acid (HA) and tissue-type plasminogen activator (t-PA), as well as those of the erbB2 oncoprotein, epidermal growth factor receptor (EGFR), HA, CD44v5 and CD44v6 in the cell membrane fraction. Likewise, we considered size, ploidy, S-phase fraction and axillary node involvement as variables of the study. The transition from HG1 to HG2 and from HG2 to HG3 was accompanied by a number of common features: global increase in size, greater number of tumors >2.0 cm, decrease in membrane hyaluronic acid concentrations, increased cell proliferation (S-phase >7%) and greater aneuploidy. Other events observed during the transition from HG2 to HG3 were a decrease in ER, PR, t-PA and cytosolic hyaluronic acid. These results led us to consider that HG is associated with certain clinical-biological changes that may help explain its value as a prognostic factor in breast carcinomas.
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PMID:Histological grade in breast cancer: association with clinical and biological features in a series of 229 patients. 1128 57

Breast cancer screening is important for the early detection of breast cancer. Tumors that become symptomatic in the screening interval are known as interval cancers but the reasons for their rapid progression are unknown. Estrogen receptor expression is lower in interval cancers suggesting that they may have reduced hormonal responsiveness. To investigate this hypothesis we have measured the expression of the estrogen receptor and three estrogen-responsive genes (cathepsin D, progesterone receptor, and TFF1) in screen-detected and interval breast cancers. The expression of the protease cathepsin D was not associated with estrogen receptor in either group of tumor. Progesterone receptor expression was highly correlated with that of the estrogen receptor in both groups of tumors but it was not expressed at significantly different levels in the two groups of tumors. Expression of TFF1, a cellular motogen, was correlated with estrogen receptor in screen-detected but not interval cancers and was expressed at markedly higher levels in interval breast tumors, the group that expresses lower levels of estrogen receptor. Interval cancers are characterized by high levels of expression of TFF1 and/or Ki67 suggesting that cell migration and cell division play important roles in the rapid progression of interval cancers. The observation that TFF1 expression in interval cancers tends to be estrogen-independent and that interval cancers have reduced estrogen receptor expression suggests they may have a reduced response to hormone therapy.
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PMID:High expression of the trefoil protein TFF1 in interval breast cancers. 1143 68

The paper presents recent data on the role of oncogenes and suppressive genes, receptors of steroidal hormones, secretory protein pS2, cathepsin D, urokinase and tissue plasminogen activators and their inhibitor PAI-I, polypeptide growth factors and somatostatin and their receptors in the evaluation of proliferative activity and drug therapy responses and in the prediction of disease and on the simultaneous estimation of the limited number of mutually complementing parameters that can characterize the proliferative activity of a tumor, its metastatic potential and sensitivity to different types of overall and regional regulation. The main task for investigators engaged in this area is to choose a qualitatively and quantitatively optimal ratio of molecular markers of breast cancer to evaluate the biological behavior of a tumor.
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PMID:[Modern prospects for molecular-biochemical methods for evaluating biological "behavior" of breast neoplasms]. 1167 60

There is ample information on the clinical role of biologic factors in female breast cancer: urokinase-type plasminogen activator (uPA), its receptor uPAR, its inhibitors PAI-1 and PAI-2, cathepsin D and pS2-protein. However such reports are missing or very rare for male breast cancer. We determined the cytosolic levels of oestrogen receptor (ER), progesterone receptor (PgR), cathepsin D, pS2-protein, uPA, uPAR, PAI-1 and PAI-2 of the primary tumour tissues from 40 male breast cancer patients. The tumour levels were compared with those of 180 matched females and 4114 historic females with breast cancer. In male breast tumours the level of PgR was higher, those of uPA, PAI-1, PAI-2 and cathepsin D lower. The tumour level of ER in men was similar to those in the matched and postmenopausal women, but much higher than those in the historic women. Male breast cancer seems to be biologically different from female breast cancer. Correlation of the eight cell biologic factors with disease outcome showed that PAI-1 (p = 0.03) was the only independent predictive factor for poor prognosis in male breast cancer.
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PMID:Clinical relevance of biologic factors in male breast cancer. 1172 61

Intranasal administration of hormone replacement therapy presents an original plasma kinetic profile with transient estrogen levels giving rise to the concept of pulsed therapy. To further understand the molecular effects of this new therapy, we have compared the effects of pulsed and continuous estradiol treatments on two critical aspects of estradiol action: gene expression and cell proliferation. Cells were stimulated with estradiol as 1-h pulsed or 24-h continuous treatments at concentrations such that the 24-h exposure (concentration x time) was identical in both conditions. In MCF7 cells, the transcriptional activity of estrogen receptors (ER) on a transiently transfected responsive estrogen response element-luciferase reporter construct was shown to be drastically (approximately 10-fold) and similarly stimulated after both treatments. Moreover, the increased mRNA expression of three representative estradiol-sensitive genes (pS2, cathepsin D, progesterone receptor), evaluated by Northern blot, was identical after 1-h pulse with 7 nM estradiol or continuous treatment with 0.29 nM estradiol with the same kinetic profile over 48 h. Proliferation was quantified by a histomorphometric method on primary cultures of human normal breast cells from reduction mammoplasties and using a fluorescence DNA assay in six human breast cancer cell lines which were ER positive or negative. After a 7-day treatment period, estradiol had no effect on the proliferation of the three ER negative cell lines (BT20, MDA MB231, SK BR3) but significantly stimulated the proliferation of the normal cells and of the three tumoral hormone-sensitive cell lines (MCF7, T47D, ZR 75-1); both hormone treatments producing the same increases in cell growth. In conclusion, we have shown that the genomic or proliferative effects of estradiol were identical with pulsed or continuous treatments, thus indicating that estrogenic effects are not strictly related to concentrations but rather to total hormone exposure.
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PMID:Comparative activity of pulsed or continuous estradiol exposure on gene expression and proliferation of normal and tumoral human breast cells. 1206 83

To explore the hypothesis that aging not only increases breast cancer incidence but also alters breast cancer biology, we correlated patient age and diagnosis with tumor histology, stage and biomarkers independently determined from two different tumor archives: an American collection of approximately 800 paraffin-embedded and immunohistochemically analyzed primary breast cancers, and an European collection of approximately 3000 cryobanked primary breast cancers analyzed by ligand-binding and enzyme immunoassay (EIA). The prognostic biomarkers chosen for comparison represented surrogate measures of tumor: (i). proliferation, growth and genetic instability (mitotic and apoptotic indices, Ki-67/MIB-1-positivity, nuclear grade, p53-positivity), (ii). endocrine-dependence (estrogen receptor (ER), progesterone receptors (PR), pS2, Bcl2), (iii). growth factor receptor-dependence (ErbB2, EGFR/ErbB1), and (iv). angiogenic, invasive and proteolytic potential (uPA, PAI-1, Cathepsin D, VEGF). No biomarker reflecting tumor angiogenic, invasive or proteolytic potential showed a significant correlation with patient age at diagnosis. In contrast, significant inverse correlations (|r|>0.1; P< or =0.05) were observed for all measures of tumor growth and genetic instability as well as growth factor receptor overexpression (ErbB2 or EGFR positivity). Only one marker of endocrine-dependence, ER expression, showed a significant positive correlation with patient age at diagnosis. In summary, these findings support the hypothesis that breast cancer biology is significantly affected by patient age. In particular, breast tumors arising in older patients have slower growth rates, are more likely to be ER-positive, and are less likely to be p53-positive, EGFR-positive or ErbB2-positive.
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PMID:Age-associated biomarker profiles of human breast cancer. 1220 28

Our study attempts to determine the prognostic value of the quantitative measurement of the oncoprotein p185(Her-2/neu) in a group of patients with breast cancer and positive node involvement. In a series of 217 patients with breast cancer and positive nodes in whom the oncoprotein p185 was quantitatively determined by ELISA, we analyzed the clinico-pathological variables including age, menopausal status, tumor size, number of affected nodes, type and histology grade and the molecular variables such as the oestrogen and progesterone receptors (ER and PR, respectively), pS2 and Cathepsin D (CD). Using 260 fmol/mg protein as a cut-off point, 18% of the tumors presented as overexpressing p185. The p185 showed no relationship with any of the clinico-pathological variables studied except that its concentration was elevated in ductal and lobular histology types and in the moderate and poorly differentiated histology grades. With a median follow-up of 50 months (range 1-90), the univariate analysis of disease-free survival (DFS) and overall survival (OS) showed that the histology grade, tumor size, the number of infiltrated nodes, the p185 and the ER were the variables associated with the clinical course of the disease in the patients. In the multivariate analysis, however, only the tumor size, number of affected ganglia, the p185 and the ER remained associated with the clinical progression of the disease. The patients with p185 overexpression had a risk, not only of relapse but also death from the disease, of more than twice that of the patients who had normal p185 concentrations. When the p185 was divided into 3 categories based on +/-1 x SD above or below the mean, the patients with high and low p185 showed, in the univariate analysis, a similar relationship with DFS but not with OS. In the multivariate analysis, both with the DFS as with the OS, only a high p185 concentration retained its association with the clinical course of the disease in the patients. Our results suggest that by quantitatively determining (using ELISA) the p185 oncoprotein, groups of cancer patients of high risk could be better identified for more effective clinical management.
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PMID:Prognostic value of the quantitative measurement of the oncoprotein p185(Her-2/neu) in a group of patients with breast cancer and positive node involvement. 1223 94

We showed previously that prolonged treatment of a MCF-7-derived cell line with hydroxytamoxifen (OHT) induces the irreversible silencing of some estrogen-responsive genes, whereas OHT-resistant cell growth appears simultaneously (E. Badia et al., Cancer Res., 60: 4130-4138, 2000). Based on the hypothesis that particular gene silencings could be involved in triggering the resistance phenomenon, we focused our study on the mechanism of OHT-induced silencing. More precisely, we wished to determine to what extent the recruited histone deacetylase (HDAC) activity, which is known to be involved in the repressive effect induced by antagonist ligands of nuclear receptors, could participate in various aspects of OHT effects, particularly in gene silencing. A fusion protein (HDAC-EG) of human HDAC1 fused with the estrogen receptor DNA-binding domain and the glucocorticoid receptor ligand-binding domain allowed targeting of chimeric HDAC1 activity on estrogen-responsive elements (EREs) in the presence of glucocorticoid ligands. When HDAC-EG was transiently expressed in HeLa cells together with estrogen receptor, an antiestrogen-like effect was obtained on an ERE-controlled luciferase reporter gene in the presence of agonist or antagonist glucocorticoids. In MCF-7-derived cells stably expressing HDAC-EG and an estrogen-regulated luciferase, liganded HDAC-EG again produced an antiestrogenic effect on expression of natural estrogen-regulated genes such as pS2, progesterone receptor, and cathepsin D and cell growth together with chimeric luciferase gene expression. However, a prolonged HDAC-EG-mediated antiestrogen effect did not lead to irreversible luciferase gene silencing, as OHT does. It nevertheless accelerated the OHT-driven phenomenon. The antiestrogen effect of OHT thus differs from that of an ERE-targeted HDAC1 activity that might participate in irreversible silencing but is not sufficient to trigger it.
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PMID:An estrogen-responsive element-targeted histone deacetylase enzyme has an antiestrogen activity that differs from that of hydroxytamoxifen. 1243 46

Breast cancer incidence increases with age but this relationship has not been fully explored with regard to expression of estrogen receptor (ER) and ER-inducible genes (PR, pS2, Bcl2, cathepsin D), or the age-dependence of oxidant stress markers that also affect ER-inducible gene expression. In this three-part study, we first correlated age at diagnosis with expression of breast cancer markers ER, PR, pS2, Bcl2, and cathepsin D, quantitated by enzyme immunoassays from a European collective of approximately 3000 cryobanked primary breast cancers and approximately 300 adjacent non-malignant breast tissues. Results were then compared with ER and PR data reported to the SEER registry for 83,541 US cancers diagnosed during 1992-1997. Lastly, a homogeneous subset of 70 ER-positive tumors preselected from the European collective was blindly analyzed for age-specific changes in the DNA-binding content of redox-sensitive transcriprtion factors, AP1 and Sp1, and the oxidant stress-activated protein kinase, phosphorylated(P)-Erk5. Increases in breast tumor ER from patients aged <30 to >80 years mirrored 10-fold lower increases in non-malignant breast tissue ER content up to age 60, rising faster thereafter and reaching a near 25-fold differential between malignant and non-malignant breast tissue by age 80. ER-inducible markers PR, pS2, Bcl2, and cathepsin D were overexpressed in tumors relative to non-malignant breast tissue but, unlike ER, did not increase with patient age. While SEER data demonstrated that the increase in US breast cancer incidence rates after age 50 is confined to ER-positive tumors in patients of all ethnic subsets, these patients also showed a striking increase in the proportion of higher-risk ER-positive/PR-negative breast cancers arising after age 50. Mechanistically essential for ER-inducible PR expression, Sp1 DNA-binding function (but not Sp1 content) was lost with age in ER-positive tumors; and this functional defect correlated with increased tumor content of the oxidant stress marker, P-Erk5. Altogether these findings support two hypotheses: (i) dysregulated ER expression underlies the age-specific increase in breast cancer incidence after age 50; and (ii) oxidative stress and loss of Sp1 DNA-binding may contribute to an increasing incidence in higher-risk ER-positive/PR-negative breast cancers with aging.
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PMID:Age-dependent changes in breast cancer hormone receptors and oxidant stress markers. 1246 83


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