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 authors immunohistochemically studied the expression of the estrogen receptor (ER), 27-kD heat shock protein (HSP27) and pS2 in 118 invasive primary human breast cancers. Positive nuclear staining of the ER was detected in 64% of the cases and was closely correlated with the biochemical assay (p < 0.0001). ER-positive tumors were significantly decreased with tumor size and stage (p < 0.001 each), but not with lymph node status. Positivity of the ER was correlated with the cytoplasmic expression of HSP27 (p < 0.005), pS2 (not significant) and HSP70 (not significant). ER negativity was significantly correlated with the expression of p53, epidermal growth factor receptor (EGFR) and c-erbB-2 (p < 0.05 each). Thus, it was concluded that ER-positive breast carcinomas, relatively small in size, preferentially expressed HSP27, HSP70 and pS2 and that ER-negative tumors, relatively large in size, were predisposed to express p53, EGFR and c-erbB-2.
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PMID:Immunohistochemical detection of estrogen receptor in invasive human breast cancer: correlation with heat shock proteins, pS2 and oncogene products. 763 53

A third of breast cancers are estrogen dependent and respond to endocrine therapy. The estrogen receptor (ER) was the first marker used to predict the responses to treatment, and two-thirds of ER positive tumors show a favourable response. Several estrogen-regulated proteins were further studied in a search to enhance the prediction accuracy of ER status: progesterone receptors, 24-K heat shock protein, cathepsin D, and recently pS2 protein. The pS2 gene, also named BCEI, pNR-2 [4], Md2, was first identified by two groups using differential screening of a complementary DNA library derived from a human breast carcinoma cell line (MCF-7) grown with and without estrogens. Later on two independent English groups and a Japanese group identified a gene similar to pS2. The pS2 mRNA, relatively abundant (0.8%) in the MCF-7 cell line when stimulated by estrogens, encodes a cystein-rich, 84 aminoacids peptide which is secreted by breast cancer cells. The expression of the pS2 gene, pS2 protein assays in tumor cytosols and more recently pS2 detection by immunocytochemistry, have been described in several series of breast cancers.
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PMID:Clinical significance of the estrogen regulated pS2 protein in mammary tumors. 824 Jul 4

This study examined whether levels of estrogen receptor (ER), progesterone receptor (PR), and expression of estrogen regulated pS2 and/or heat shock protein (hsp) 27 were associated with drug resistance in a series of MCF-7 sublines expressing modest (i.e. 3- to 14-fold), yet clinically relevant, levels of resistance to vincristine (VCR). These sublines were variously derived following pulsed exposures to VCR, to fractionated X-irradiation, or to alternating drug and X-ray treatments. This selection procedure more closely reflects the clinical treatment of breast tumors than the use of continuous drug exposures. The drug-selected sublines exhibited the classical multidrug resistance phenotype (MDR) characterized by cross-resistance to vinblastine (VLB), etoposide (VP-16), and Adriamycin (ADR), overexpression of P-glycoprotein (Pgp), impaired accumulation of [3H]-VCR and of Rhodamine-123 (Rh 123), and altered activities of certain drug detoxification enzymes. This classic MDR phenotype was associated with a lack of mitogenic response to estrogen or antiestrogen, related to loss of detectable ER and PR; consistent with these data, neither pS2 nor hsp27 expression was detectable. In contrast, X-ray-pretreated VCR-resistant cells (MCF/DXR-10) cells exhibited a distinctive resistance phenotype proving cross-resistant to VLB and VP-16 but not to ADR, and Pgp overexpression was not detectable. Furthermore, these VCR-resistant DXR-10 cells retained parental levels of ER and PR, exhibited sensitivity to estrogen and 4-hydroxytamoxifen, and expressed detectable levels of pS2 and hsp27. Comparable characteristics to these MCF-7/DXR-10 cells were also identified in a similarly-derived X-ray-pretreated VCR-resistant subline of the ZR-75-1 human breast tumor cell line. These data therefore indicate that functional ER are frequently, but not invariably, modified in tumor cells which express resistance to multiple drugs.
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PMID:Differential expression of steroid receptors, hsp27, and pS2 in a series of drug resistant human breast tumor cell lines derived following exposure to antitumor drugs or to fractionated X-irradiation. 840 Mar 21

The estrogen receptor (ER) is a hormone-dependent transcription factor that belongs to the steroid/thyroid hormone receptor superfamily. Since the ER contributes to development and progression in human breast cancer, a number of studies have explored ways to inactivate this receptor. Previous studies have suggested that the 90-kDa heat shock protein (Hsp90) interacts with the ER, thus stabilizing the receptor in an inactive state. Here, we report that radicicol, an Hsp90-specific inhibitor, repressed estrogen-dependent transactivation of the ER as measured by pS2 gene transcription and a reporter gene encoding an estrogen-responsive element. Furthermore, we showed that radicicol induced rapid degradation of ERalpha, while the amount of ubiquitinated ERalpha was increased. A proteasome inhibitor, LLnL, almost completely abrogated the radicicol-induced decrease in expression level, as well as in transcriptional activity of ERalpha. These results suggest that radicicol disrupts the ER-Hsp90 heterodimeric complex, thereby generating ERalpha that is susceptible to ubiquitin/proteasome-induced degradation.
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PMID:Radicicol represses the transcriptional function of the estrogen receptor by suppressing the stabilization of the receptor by heat shock protein 90. 1191 45