Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The promoter region of the epidermal growth factor (EGF) receptor has been identified by in vitro transcription using EGF receptor genomic DNA fragments as template and by primer extension and nuclease S1 mapping using EGF receptor mRNA. Six transcriptional start sites were identified. DNA sequence analysis shows that the promoter region contains neither a "TATA box" nor a "CAAT box," has an extremely high G+C content (88%), and contains five CCGCCC repeats and four (TCC)TCCTCCTCC repeats. This promoter region is situated close to or within a DNase I-hypersensitive site in A431 human epidermoid carcinoma cells, which overproduce the EGF receptor. The EGF receptor gene promoter has some resemblance to the promoter of the hydroxymethylglutaryl-CoA reductase gene and the early promoter of simian virus 40. This similarity may offer a clue to the mechanism by which the receptor gene is regulated.
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PMID:Characterization and sequence of the promoter region of the human epidermal growth factor receptor gene. 299 99

Twenty-one invasive squamous-cell carcinomas (SCC) of the bladder from Schistosoma-hematobium-infected patients were examined immunohistochemically for the expression of p53, Rb, EGFR and c-erbB-2 proteins; and screened by single-strand conformation polymorphism and sequencing for mutations in the ras (H, N, K) codon hotspots (12, 13, 61) and p53 (exons 4-9) genes. Positive staining for p53, EGFR and c-erbB-2 was reported in 38, 67 and 28% of tumors respectively. Only one of the tumors, the only one that was poorly differentiated, displayed an absence of nuclear Rb staining. Ras alterations were detected in the H-ras gene in 3 tumors, 2 of which harbored a codon-13 (Gly-->Arg) and one a codon-12 (Gly-->Ser) point mutation. p53 mutations were recorded in 12 tumors (57%), 6 of which stained positively for p53. Four tumors had exon-7 mutations (codons 235, 241 and 249; one tumor had 2 exon-7 mutations). Eight tumors were mutated in exon 8 (codons 264, 271, 273, 285, 286, 288 and 294), 5 of which harbored multiple mutations. One tumor had an insertion/deletion event in exon 9. The frequency of detection of over-expression of EGFR and c-erbB-2 in bilharzial-bladder lesions is comparable to that reported in TCC, contrasting with the infrequent loss of Rb expression found in invasive lesions associated with schistosomiasis infection. However, the detection of multiple p53 mutations in these lesions is suggestive of the involvement of a carcinogenic agent with maintenance of preferential activation of the H-ras gene.
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PMID:Molecular events underlying schistosomiasis-related bladder cancer. 762 66

In this paper the predictive value of molecular prognostic parameters for bladder cancer is discussed. DNA ploidy has additional prognostic value for grade 2 tumors, irrespective of stage, with aneuploid tumors having a poor prognosis. Overexpression of the epidermal growth factor receptor (EGFR) can be used as a prognostic factor for the group of superficial tumors. Both abnormal E-cadherin and retinoblastoma (RB) expression have additional prognostic value for invasive tumors. The exact predictive value for the superficial tumors needs further study. The results with respect to p53 are conflicting and its exact role especially in the progression of pT1g3 tumors has to be clarified. In view of the discordance concerning its prognostic value, c-erbB-2 overexpression also needs further study. It appears that at this moment only a few molecular markers seem to have potential prognostic value, but their precise clinical relevance has to be studied more extensively. In particular the value of progression markers in the superficial TCC needs more attention.
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PMID:Molecular prognostic factors in bladder cancer. 791 39

Bacillus Calmette Guerin (BCG) is generally regarded as an effective immunotherapy for superficially invasive papillary transitional cell carcinoma of the bladder. The exact mechanism(s) which underlie its efficacy are unknown. As C-erbB-2 oncoprotein and vascular endothelial growth factor (VEGF) have been shown to be over-expressed in TCC of the bladder, it has been postulated that they may be important in its pathogenesis. The purpose of this study was to 1.) differentially evaluate the effect of BCG immunotherapy in treated and untreated cohorts on the immunohistochemical expression of C-erbB-2 and VEGF in formalin-fixed paraffin-embedded sections of superficial and superficially invasive (Stage Ta-T1) transitional cell carcinoma of the bladder. Immunolabeling intensity was assessed independently by two pathologists and reported as a mean labeling index. The results confirm previous studies that 1.) both c-erbB-2 and VEGF are over-expressed in these tumors MLI = 90.1 and 45.7 respectively, 2.) that VEGF is an early and sensitive indicator of TCC, and 3.) that BCG has a salutary effect on papillary TCC, 66% vs. 89% recurrence rate, P = .04. Our findings show that 1.) C-erbB-2 expression is decreased in patients tumors which show response to BCG (45.7 to 38.5), P = 0.15, 2.) that BCG administration has no effect on the expression of VEGF. While the decrement in c-erbB-2 immunostaining observed in those patients who received BCG contrasts with the increase in c-erbB-2 immunolabeling observed in patients who did not receive BCG, the differences were not statistically significant and could reflect tumor grade or stage regression associated with BCG therapy. However, this study suggests that BCG differentially influences the expression of C-erbB-2 and VEGF.
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PMID:Differential C-erbB-2 and VEGF expression following BCG immunotherapy in superficial papillary transitional cell carcinoma of the bladder. 1247 25

Gene amplification or HER-2/neu protein overexpression signals a poor outcome for bladder cancer patients. We investigated the anti-proliferative effect of IFN-gamma in HER-2/neu-transfected human bladder cancer cells (TCC-N5 and TCC-N10). The cells continued growing after IFN-gamma stimulation but did not activate the Janus kinase (Jak)/Stat pathway. We found Jak/Stat protein phosphatase in TCC-N5 and TCC-N10 cells with upregulated Src homology 2-containing protein tyrosine phosphatase-2 (SHP-2). After the cells had been treated with AG825, a HER-2/neu-specific inhibitor, SHP-2 expression declined, and Jak2/Stat1 reactivated. Similar results were reported in a mouse bladder cancer cell line, MBT2, with constitutive HER-2/neu overexpression. Further, AG825 pretreatment restored the anti-proliferation activity of IFN-gamma in TCC-N5 and TCC-N10 cells. Therefore, the suppression of IFN-gamma signaling in HER-2/neu-overexpressing bladder cancer cells might be due to SHP-2 upregulation. The regulation of SHP-2 by HER-2/neu provides a new target for blocking the HER-2/neu oncogenic pathway.
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PMID:HER-2/neu raises SHP-2, stops IFN-gamma anti-proliferation in bladder cancer. 1734 77