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)

Expression of the calcium-dependent cell-cell adhesion molecule E-cadherin has been examined in 187 primary breast carcinomas using an immunohistochemical technique. The pattern and extent of reactivity has been correlated with clinicopathological data including tumour type, grade and lymph node status and with other prognostic parameters including oestrogen receptor (ER) status, expression of c-erbB-2, pS2 protein and epidermal growth factor receptor (EGFR). Two patterns of E-cadherin staining were observed in carcinomas, membrane reactivity and a diffuse cytoplasmic staining. A marked difference in expression of E-cadherin was observed between infiltrating lobular carcinomas (ILC) and infiltrating ductal carcinomas (IDC), the former showing complete loss of membrane staining, whereas 93% of IDC retained some level of expression. In IDC reactivity was not related to tumour grade but there was a significant association between reduced membrane levels of E-cadherin and the presence of lymph node metastasis, and a highly significant correlation between the presence of cytoplasmic E-cadherin and metastasis. A significant relationship was also demonstrated between reduced E-cadherin reactivity and expression of EGFR. These findings emphasise the complexity of control of E-cadherin in breast carcinomas and provide evidence of a link between membrane signalling pathways and modulation of E-cadherin expression.
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PMID:E-cadherin relates to EGFR expression and lymph node metastasis in primary breast carcinoma. 888 10

Estrogen receptors (ERs) are a recognized prognostic factor and therapeutic target in breast cancer. The loss of ER expression relates to poor prognosis, poor clinical outcome and impairs the use of anti-estrogenic treatment. Histone deacetylase inhibitors are candidate drugs for cancer therapy. Among them, valproic acid (VPA) is a long used and safe anti-epileptic drug. We studied the biological consequences of the chromatin remodeling action of VPA in a normal human mammary epithelial cell line and in ERalpha-positive and ERalpha-negative breast cancer cell lines. In these cells and regardless of their ER status, VPA-induced cell differentiation, as shown by increased milk lipids production, decreased expression of the CD44 antigen and growth arrest in the G(0)-G(1) phase of the cell cycle. These effects were accompanied by decreased Rb phosphorylation, hyperacetylation of the p21(WAF1/CIP1) gene promoter and increased p21 protein expression. Only in breast cancer cells, cyclin B1 expression was decreased and the cells accumulated also in G(2). ERalpha expression decreased in ERalpha-positive, increased in ERalpha-negative and was unchanged in normal mammary epithelial cells, as did the expression of progesterone receptor, a physiological ERalpha target. VPA decreased the expression of the invasiveness marker pS2 in ERalpha-positive breast cancer cells, but did not cause its re-expression in ERalpha-negative cells. Overall, these data suggest that in both ERalpha-positive and -negative malignant mammary epithelial cells VPA reprograms the cells to a more differentiated and "physiologic" phenotype that may improve the sensitivity to endocrine therapy and/or chemotherapy in breast cancer patients.
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PMID:Epigenetic reprogramming of breast cancer cells by valproic acid occurs regardless of estrogen receptor status. 1878 98