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 HER2/neu protooncogene encodes a transmembrane receptor tyrosine kinase of Mr185 kDa (called p185) which is structurally and functionally homologous to the epidermal growth factor receptor. Shc proteins are important downstream signal transducers of receptor tyrosine kinases. We reported here a novel finding that p66Sch was absent or nearly absent in p185-overexpressing breast cancer cells. This inverse correlation of p185 overexpression and p66Shc expression is probably specific to breast cancer cells because this phenomenon was not observed in p185-overexpressing human ovarian, lung, or oral cancer cells, or mouse fibroblast cells. In contrast, the p52Shc and p46Shc isoforms were expressed at similar levels in both p185-overexpressing and p185 basal level breast cancer cell lines. Furthermore, tyrosine phosphorylation of p52Shc and p46Shc and subsequent formation of Shc/Grb2 complex were detected in breast cancer cells in which the p185 tyrosine kinase is activated, indicating that p66Shc is not required for mediating the HER-2/neu signaling pathway in breast cancer cells.
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PMID:p66Shc isoform down-regulated and not required for HER-2/neu signaling pathway in human breast cancer cell lines with HER-2/neu overexpression. 866 Mar 24

The protease catalyzing the hydrolysis of the tripeptide fluorescence substrate, butoxycarbonyl-valine-proline-arginine-(7-amino-4-methylcoumarin) (Boc-Val-Pro-Arg-MCA) and the neu oncogenic protein are potentially useful biomarkers for human cancer prevention studies. In the present study, we standardized a specific substrate hydrolysis method for measuring this protease activity in human oral mucosal cells and characterized the relationship between neu oncogene expression and protease activity in patients enrolled in an oral cancer prevention trial using Bowman Birk Inhibitor Concentrate (BBIC) as the cancer preventive agent. The results demonstrate that changes in the protease activity in oral mucosal cells after BBIC treatment correlated with the changes in the neu protein levels in oral mucosal cells (r = 0.726, P < 0.001) and serum (r = 0.675, P < 0.001), suggesting that the Boc-Val-Pro-Arg-MCA hydrolyzing activity can be as useful as neu oncogene expression as a cancer biomarker. In the 25 patients enrolled in the study, the level of neu protein in oral mucosal cells correlated with the serum neu protein concentration in the patients before BBIC treatment (r = 0.645, P < 0.001). However, such a correlation was not observed after the BBIC treatment, suggesting that BBI may inhibit serine protease(s) involved in the cleavage of neu protein on the cell surface, thereby preventing the release of the extracellular domain of neu protein into the circulation. By inhibiting the cleavage of neu protein on the cell surface, BBI could prevent malignant and premalignant cells expressing high levels of neu protein antigen from escaping host immunological surveillance control.
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PMID:Relationship between protease activity and neu oncogene expression in patients with oral leukoplakia treated with the Bowman Birk Inhibitor. 1042 97

In the current study, we examined the clinical characteristics and survival probability rates of 116 patients treated for squamous cell carcinoma (SCC) of the tongue. In 55 randomly selected patients these data were correlated with the immunohistological analysis of the tumor and apoptosis-related markers, p53, Bcl-2, c-erbB-2 (Her-2/neu), and to the apoptosis rate assessment by the terminal dUTP nick-end-labeling (TUNEL) method. The overall 5-year survival probability was 55%, which might be the result of the low incidence of smoking and/or alcohol consumption among the patients (21%), the early diagnosis (65% at Stages I-II) and the low histological grades (91% good-moderate). Radiotherapeutic or surgical treatment of the neck did not alter the survival probability achieved by local surgery for Stage I patients, but significantly improved survival for Stage II patients. Independent tumor-related variables which significantly worsened the probability of survival were found. Concomitant non-oral cancer was found to be a poor variable for prognosis prediction. Positive staining of p53, TUNEL (apoptosis rate), c-erbB-2 and Bcl-2 was found in 60, 48, 18 and 15% of the lesions, respectively (P<0.0001). The possible biological significance of these markers in tongue SCC is discussed in relation to the current literature, and an independent role for TUNEL and p53 is suggested.
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PMID:Squamous cell carcinoma of the tongue: the prevalence and prognostic roles of p53, Bcl-2, c-erbB-2 and apoptotic rate as related to clinical and pathological characteristics in a retrospective study. 1221 83

Oral cancer is a serious problem growing in incidence in many parts of the world; it is considered the sixth most common cancer and despite sophisticated surgical and radiotherapeutic modalities, oral squamous cell carcinoma, which represents 90% of oral cancers, is characterized by poor prognosis and a low survival rate. The Epidermal growth factor receptor family of receptor tyrosine kinases (RTK) comprises of four distinct receptors: the EGFR (also known as ErbB-1/HER1), ErbB-2 (neu, HER2), ErbB-3 (HER3) and ErbB-4 (HER4). Several studies have been published on the role of EGFR in the pathogenesis of oral carcinoma. The aim of the present review is to describe the role of EGFR pathway in oral cancer with special focus on its role during the carcinogenesis process as a result of therapeutic approaches of EGFR in oral cancer. The EGFR is a 170-kDa cell-surface protein involved in many biological processes, such as proliferation, migration, DNA synthesis and adhesion. Overexpression of EGFR results in a poor prognosis in oral cancer and its activation is associated with the malignant phenotype, inhibition of apoptosis and increased metastatic potential. EGFR variations and mutations have been correlated with tumor formation, and possibly alter the therapeutic efficacy of EGFR inhibitors.
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PMID:Effective targeting of the epidermal growth factor receptor (EGFR) for treating oral cancer: a promising approach. 2469 81