Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The progression of human breast cancer is often associated with a loss of estrogen dependence for growth, a resistance to estrogen antagonists such as tamoxifen, and the metastatic spread of the disease to secondary sites. Cell lines developed from such advanced breast tumors are often metastatic in athymic mice, show a loss of estrogen receptor mRNA and protein (ER-), and do not respond to 17beta-estradiol. However many advanced human breast tumors do express significant amounts of ER transcript, especially when analyzed by more sensitive methods of detection including RT-PCR and Ribonuclease Protection Assay (RPA). No metastatic, ER+breast tumor cell line has previously existed to examine the role of ER in metastatic progression and acquired drug (tamoxifen) resistance. The GI-101A cell line was recently developed from a metastatic breast tumor xenograft and is both tumorogenic and metastatic to the lungs and lymph node when injected into athymic mice, a pattern similar to that seen in patients. While Western blot analysis initially indicated that GI-101A was ER-, analysis of ER mRNA by RT-PCR and RPA have demonstrated the expression of ER (as well as EGF receptor and neu oncogene) transcripts. Functional ER in GI-101A was confirmed by a clear growth response to 17beta-estradiol in culture. Optimal 17beta-estradiol concentrations were significantly lower for GI101A than for MCF-7 (1 n m as opposed to >/=10 n m), and GI-101A growth was inhibited at 17beta-estradiol concentrations above 10 n m. Unlike MCF-7 cells, GI-101A shows constitutive expression of pS2 protein in hormone depleted media with no apparent induction by 17beta-estradiol supplimentation, as well as a resistance to the anti-estrogen tamoxifen at concentrations up to 10 n m. Finally, ER transcripts which likely represent an alternately spliced ER variant which has previously been shown to encode a constitutively active ER protein have been detected in GI-101A at levels similar to the wild type transcript, and offer a possible mechanism for estrogen independence, tamoxifen resistance, and constitutive pS2 expression.
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PMID:A metastatic breast tumor cell line, GI-101A, is estrogen receptor positive and responsive to estrogen but resistant to tamoxifen. 1032 49

Tamoxifen treatment substantially improves the 10-year survival of women with estrogen-receptor (ER)-alpha-positive tumors. However, approximately one-third of all breast cancer patients with ER-alpha-positive tumors progress on antiestrogen therapy. The molecular mechanism(s) involved in antiestrogen-resistant phenotype of breast carcinoma is not completely understood. The PTEN (phosphatase and tensin homolog deleted on chromosome Ten) gene is a novel candidate tumor suppressor that plays an important role in cell cycle regulation and apoptosis by regulating Protein kinase-B/Akt activity. Previous studies have shown that PTEN downregulation in breast cancer is associated with high-grade tumor, distant metastases and poorer disease-free survival. Decreased PTEN and/or increased protein kinase B/Akt activity in breast cancer cells has recently been associated with resistance to tamoxifen-induced apoptosis. In this study, we have evaluated PTEN expression by immunohistochemistry in 100 tamoxifen-treated ER-alpha-positive breast cancer patients. Reduced PTEN protein expression was associated with shorter relapse-free survival. When stage I patients were analyzed separately, reduced PTEN expression was a strong predictor of both, shorter relapse-free survival and shorter disease-specific survival. An association of reduced PTEN expression with shorter relapse-free survival and disease-specific survival in stage I patients was still observed after stratification by stage, axillary lymph node status, tumor size, grade, and expression of ER-alpha, progesterone receptor, and Her-2/neu. In summary, our results showed a strong association between downregulation of PTEN expression in ER-alpha-positive tumors and failure to tamoxifen treatment.
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PMID:Reduced PTEN expression predicts relapse in patients with breast carcinoma treated by tamoxifen. 1547 31

Androgen receptor (AR) is known to be expressed in approximately 70 to 90% of invasive breast cancers, but there are still conflicting data in terms of AR expression in ductal carcinoma in situ (DCIS). The aim of this study was to evaluate AR expression in DCIS and to compare these results with nuclear grading and with other common endocrine-related markers. On this basis the authors performed immunohistochemical staining for estrogen receptor (ER)-alpha and ER-beta, progesterone receptor (PR), pS2, her-2/neu, and AR in 59 cases of DCIS (24 low grade, 5 intermediate grade, 30 high grade). They found a strong correlation of expression of ER-alpha (P=0.003), PR (P<0.0001), and nuclear grading. For AR expression, 44.1% of all DCIS were positive, but there was no correlation between nuclear grading (P=0.535) and the expression of the other factors. The authors conclude that AR expression in DCIS is not correlated with nuclear grading and with the expression of other known endocrine-related markers such as ER-alpha and -beta, PR, pS2, and her-2/neu. The immunohistochemical assessment of AR status, therefore, may not help in providing a more objective way of classifying DCIS.
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PMID:Androgen receptor expression in ductal carcinoma in situ of the breast: not a helpful marker for classification such as estrogen receptor alpha and progesterone receptor. 1572 90

Precursors and preinvasive lesions of the breast include atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and lobular neoplasia (LN). There is a significant debate regarding the classification, diagnosis, prognosis and management of these lesions. This review article describes the current theories regarding the pathogenesis and molecular evolution of these lesions. It reviews the implication of a variety of molecules in the continuum of breast lesions: estrogen receptors (ER-alpha and ER-beta), c-erb-B2 (Her2/neu), p53, Ki-67, bcl-2, E-cadherin, transforming growth factor-beta (TGF-beta), p27 (Kip1), p16 (INK4a), p21 (Waf1), vascular endothelial growth factor (VEGF). With respect to the aforementioned molecules, this article reviews their pathophysiological importance, and puts the stress on whether they confer additional risk for invasive breast cancer or not. This knowledge has the potential to be of importance in the therapeutic decisions presenting in the common clinical practice.
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PMID:Precursors and preinvasive lesions of the breast: the role of molecular prognostic markers in the diagnostic and therapeutic dilemma. 1754 32