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)

The synthesis of pS2 protein is induced through estrogen-dependent transcription of the pS2 gene. The presence of the pS2 protein in breast cancer is thought to be as valuable as receptor status, or even more so, in predicting the response to hormonal therapy. Furthermore, pS2 appears to be a prognostic factor for primary breast cancer. In 162 cases of primary breast cancer, pS2 was tested by immunohistochemical procedures on formalin-fixed and paraffin-embedded tissues. Staining was evaluated semi-quantitatively using an immunoreactive score (IRS). The concentrations of pS2 in tumor cytosol were determined using an immunoradiometric assay. Positive staining for pS2 (IRS > or = 2) was seen in 27% of the tumors. Comparison of immunohistochemical and biochemical detection (26% of tumors had pS2 cytosol concentrations above the cut-off value of 26 ng/mg cell protein) revealed an 81% concordance rate (r = 0.76; P < 0.0001). Univariate analysis showed no significant correlation of immunohistochemical pS2 detection and age or menopausal status of patients, tumor size, tumor grade or nodal status. However, the immunohistochemical pS2 status correlated significantly with the immunohistochemical detection of the estrogen (ER; P < 0.001) and progesterone receptor status (PR; P < 0.0001). pS2-positive tumors were ER-positive in 66% of cases and PR-positive in 73%; 89% of pS2-positive tumors were positive for ER and/or PR. The incidence of immunohistochemical pS2 detection was 41% in the group of steroid receptor positive carcinomas (ER- and/or PR-positive) in contrast to 7% in steroid receptor negative tumors (ER- and PR-negative).
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PMID:[Immunohistochemical detection of pS2 protein in paraffin sections of breast carcinoma tissue. Comparison with results of an immunoradiometry assay]. 766 10

pS2 protein assay was performed with Elsa-pS2 kit (CIS-Biointernational) on a group of 1,065 patients with operable breast cancer who underwent breast surgery in the years 1982 through 1990. The median follow-up was 57 months. This group included exclusively infiltrating ductal carcinoma with primary surgery. Age mean was 58 yr; T0-T1, 33.6%; T2-T4, 66.4%; Differentiation grade I, 29%; node negative, 53%; estrogen receptor (ER) positive, 62.4%; progesterone receptor (PR) positive, 55.2%; mean tumor size, 2.4 cm; local recurrence, 5.2%; metastasis, 17.5%. pS2 values varied from 0.1 to 707 ng/mg of cytosol protein (median, 5.6; mean 24.5; 95th percentile 112 ng/mg p). There was no significant relationship between the mean level of pS2 and age, tumor size, nodal status, whereas pS2 was related to histological grade (P < 10(-3)), ER (P < 10(-5)), and PR (P < 10(-5)). By using 2 ng/mg p as pS2 cutoff, 77/391 (19.7%) of ER+PR+ tumors were pS2-, and 122/345 (35.4%) of ER-PR-tumors were pS2+; with this cutoff, a strong relationship existed between pS2 and overall survival, but not between pS2 and relapse-free survival. With Cox multivariate analysis, pS2 protein was classified after lymph node status, histological size, ER, differentiation grade, age, clinical stage, PR. In patients with axillary lymph node involvement (N+), pS2 status could discriminate between good and bad prognosis, specially for patients with small tumors (< 2 cm) and with less than seven invaded nodes. This study showed that pS2 protein was a poor prognostic factor in comparison with classical factors.
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PMID:[PS2 as a prognostic factor in 1065 cases of human breast cancer. A multicenter study]. 770 45

The effect of structure of the estrogen ligand on the accumulation of tPA mRNA and the activity of extracellular fibrinolytic enzyme has been examined in cultures of MCF-7 cells. Estradiol(E2)-stimulated fibrinolytic activity was preceded by an increase in actinomycin D sensitive tPA mRNA synthesis which peaked at 18 h. Ten A- and D-ring structural analogs of E2 affected tPA mRNA accumulation and extracellular fibrinolytic activity. Only in the case of two A-ring isomers (2- and 4-hydroxyestratrien-17 beta-ol) was the decreased effect of the ligand's structural change on tPA mRNA accumulation and fibrinolysis not explained by a comparable decline in affinity of the ligand for estrogen receptor. Both of these analogs functioned as antiestrogens. The stimulatory capacity of androstanediols on the tPA gene required that the 3-hydroxyl group be positioned in the beta-configuration. Absence of the 17 beta-hydroxy group was beneficial to the maximum accumulation of tPA mRNA. As has been reported for other estrogen responsive genes (progesterone receptor, cathepsin D and pS2), regulation by estrogens is not related directly to the affinity of the ligand for ER, but this activity may be determined by the location of the electronegative isopotential above the A-ring of estrogenic ligands.
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PMID:Induction of tissue plasminogen activator mRNA and activity by structurally altered estrogens. 774 7

The exon 5 deletion splice variant of estrogen receptor (delta 5 ER), which in vitro is constitutively active in the absence of estrogens, may have a role in conferring both tamoxifen resistance and ER-related phenotype in breast cancer. We have investigated the expression of this variant in vivo (at the level of mRNA) in relation to known tamoxifen resistance and expression of the estrogen-regulated genes progesterone receptor (PgR) and pS2. The amount of delta 5 ER mRNA relative to wild type (WT) ER mRNA (% delta 5/WT) was assayed in 70 tamoxifen-resistant and 50 primary breast carcinomas using reverse transcription/PCR. Both WT and delta 5 ER mRNA were detected in the majority of tumors, although delta 5 ER was detected only in the presence of WT ER. Overall no significant difference was seen in % delta 5/WT ER between tamoxifen-resistant and primary control tumors (medians, 13 and 15%, respectively). Tumors in both control and resistant groups which expressed PgR/pS2 in the absence of measurable ER protein (ER- PgR+ and ER- pS2+) had significantly higher delta 5 ER mRNA levels compared with other phenotypes (P < 0.002). This association with ER-/pS2+ tumors has not been demonstrated previously. In ER+ tumors which expressed pS2, significantly greater delta 5 ER mRNA expression was observed in tamoxifen-resistant compared with control tumors (P = 0.05). A similar although nonsignificant trend was observed in ER+ PgR+ tumors. While delta 5 ER mRNA is unlikely to be responsible for tamoxifen resistance in most breast cancers, elevated delta 5 ER mRNA levels may be important in some tumors, especially those which continue to express high levels of PgR/pS2.
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PMID:Exon 5 deletion variant estrogen receptor messenger RNA expression in relation to tamoxifen resistance and progesterone receptor/pS2 status in human breast cancer. 781 59

The pathological and biological features of a consecutive series of impalpable invasive breast carcinoma, detected by mammography in the prevalent round of the breast screening programme, have been compared with a clinically presenting group of carcinomas in age-matched patients. There was a significantly higher prevalence of tubular carcinomas as well-differentiated infiltrating ductal carcinomas in the mammographically detected group, and a lower prevalence of poorly differentiated infiltrating ductal carcinomas. Lymph node metastasis was found in 6.5% of the impalpable group compared with 53% of the clinical group. The prevalence of oestrogen receptor was much higher in the impalpable group (96%) than in the control group (67%), although there were no significant differences for progesterone receptor. The prevalence of pS2 was also much higher in the impalpable group, as was cathepsin D. This finding is surprising in view of the reported relationship between cathepsin D and poorer survival. p53 and c-erb-2 proteins were detectable in fewer impalpable carcinomas. The mean MIBI (Ki-67) index was lower in the impalpable group (11.6) than in the clinical group (15.25). Within the mammographically detected group there was a significant difference in the MIBI index between tubular carcinomas and the different grades of infiltrating ductal carcinomas, with a wide range in each category but no association with size. The impalpable carcinomas detected by mammography differ from clinically presenting carcinomas in many ways, raising the question of whether a proportion or all would progress (dedifferentiate) with time.
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PMID:Pathological and biological features of mammographically detected invasive breast carcinomas. 759 62

We have previously presented data indicating the absence of estrogen and progesterone receptors from human adipose tissue by the use of specific antibodies (Abbott) as well as specific ligands. In addition, specific estrogen and progesterone cRNA probes did not hybridize to any mRNA species in either abdominal or gluteal/femoral adipose tissue as demonstrated by solution hybridization and Northern blot. In order to demonstrate even extremely small quantities of gene products we have now used the Polymerase chain reaction-technique to study estrogen- and progesterone receptor gene expression. Sequences corresponding to each specific cDNA were demonstrated indicating small amounts of estrogen- and progesterone receptor mRNA not detected by RNA/RNA or RNA/TNA (total nucleic acids) hybridization assays. The estrogen receptor-regulated gene pS2, however, was not induced by estrogens in human adipose tissue in contrast to a significant increase in pS2 mRNA levels after estrogen exposure to the estrogen receptor(+) cell line MCF7. From these results we conclude that estrogen- and progesterone receptors are absent from human adipose tissue and that the extremely low level of transcription of the corresponding genes is not sufficient to allow translation of the message into functional proteins.
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PMID:Lack of evidence for estrogen and progesterone receptors in human adipose tissue. 782 89

In this study we analysed the cytosolic concentrations of the estrogen-regulated protein pS2 in tumors of 462 breast cancer patients, 16 benign breast tumors and 58 metastases. The median pS2 values were highest in breast cancer, followed by benign tumors and metastases (Kruskal-Wallis Test: p < 0.05). Information on other prognostic factors and clinical outcome was available for 354 patients (median follow-up, 35 months). We found a pS2 value of 2 ng/mg protein to be the best cut-off level to discriminate between pS2+ (63%) and pS2- (37%) tumors with respect to relapse-free survival (RFS) and overall survival (OS). The pS2 status was significantly correlated with age, estrogen receptor (ER) and progesterone receptor (PR) status. pS2 was negatively correlated with grading and was more often positive in invasive lobular than in invasive ductal carcinomas. ER, pS2 and grading were highly significantly correlated with each other. In univariate analysis pS2- patients showed a significantly shorter RFS (p = 0.0001) and OS (p = 0.0005). However, multiple regression analysis revealed that in our series of patients the pS2 status provides no independent prognostic information.
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PMID:pS2 protein status fails to be an independent prognostic factor in an average breast cancer population. 784 May 11

The oestrogen-inducible pS2 protein has previously been associated with good prognosis for breast cancer patients. In 1987-1988 a series of 145 primary breast cancers were examined for pS2 mRNA using northern blots. On recent examination of mortality data, we were unable to find any association between tumour pS2 positivity and patient survival. One patient in 6 died within 5 years of surgery, regardless of pS2 status. In the oestrogen receptor positive/progesterone receptor positive tumour subgroup of patients, we found no evidence of increased survival for pS2-positive tumours. These results do not support use of pS2 as an indicator of increased survival in an average breast cancer patient population.
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PMID:Prognostic significance of pS2 mRNA in breast cancer. 788 Jun 21

Proliferation of the human breast tumor cell lines T47D and MCF7 was stimulated by high concentrations (10(-6) M) of the synthetic progestins gestodene and 3-ketodesogestrel, but not by Org2058, comparable to the stimulation by low dosages of estradiol (10(-10) M). At physiological concentrations of the progestins (10(-10) M) only T47D cells responded. Using specific antihormones it was shown that the effect at pharmacological dosages is mediated by a crossreaction of these compounds with the estrogen receptor (ER), while the stimulation of T47D cells at physiological concentrations seems progesterone receptor (PR) mediated. This was further substantiated using transient transfection assays with ER- and PR-inducible reporter constructs and mRNA induction of the ER- and PR-target genes pS2 and fatty acid synthetase, respectively. Using a whole cell ligand binding assay, 20-fold higher amounts of PR were measured in T47D compared to MCF7 cells. This was in line with a much higher PR-dependent transactivation in T47D cells and suggests that the level of transcriptionally active PR is a major determinant for the response to physiological concentrations of progestins in human breast cancer cells.
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PMID:Synthetic progestins induce proliferation of breast tumor cell lines via the progesterone or estrogen receptor. 792 73

Expression of the hormone-regulated genes, pS2, prolactin-inducible protein (PIP) and fatty acid synthetase (FAS), was investigated by Northern blotting in primary breast carcinoma, metastatic breast cancer in axillary lymph nodes, in uninvolved breast tissue from mastectomies and in normal lymph nodes. There were considerable differences in expression of the genes between the tissues. The proportion of tissues containing PIP-mRNA decreased from uninvolved breast tissue to primary breast carcinoma to metastatic carcinoma. The reverse applied to FAS-mRNA which was found more often in metastatic cancer than in primary cancer, and least frequently in uninvolved breast tissue. Yet another pattern was observed for pS2 expression. The highest proportion of tissues demonstrating gene expression was found in primary breast cancer with both metastatic tumor and uninvolved breast tissue expressing the gene less frequently. pS2-mRNA and PIP-mRNA could only rarely be detected in trace amounts in normal lymph nodes. In contrast, FAS-mRNA was present in about one third of normal lymph nodes. Only pS2-mRNA showed an association with estrogen and progesterone receptor status.
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PMID:Hormone-regulated genes (pS2, PIP, FAS) in breast cancer and nontumoral mammary tissue. 794 16


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