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

E-Cadherin and its undercoat proteins, alpha- and beta-Catenins, which connect cadherins to actin filaments and establish firm cell-cell adhesion, act as an invasion suppressor system. It was demonstrated that transcriptional inactivation of E-Cadherin expression occurred frequently in tumor progression, and that E-Cadherin expression in human cancer cells was regulated by CpG methylation around the promoter region. In diffusely infiltrating cancers, mutations were found in the genes for E-Cadherin and alpha- and beta-Catenins. The E-Cadherin-mediated cell-adhesion system is inactivated by tyrosine phosphorylation of beta-Catenin at the invading front of cancers with high metastatic ability. An attempt was made to identify the kinases that participate in the aberrant tyrosine phosphorylation, and c-erbB-2 protein was found to be directly associated with beta-Catenin. Transfection of N-terminally deleted beta-Catenin, which binds to c-erbB-2 but not to cadherin, markedly reduced peritoneal dissemination and hematogenous metastasis of gastrointestinal cancer cells in mouse inoculation models. Regulation of the E-Cadherin-mediated cell adhesion system by tyrosine phosphorylation of beta-Catenin is important in determining the biological properties of human cancers. Tumor cells are dissociated throughout the entire tumor masses of diffuse-type cancers, whereas those of solid tumors with high metastatic potentials are often focally dissociated or dedifferentiated at the invading fronts. Thus, both irreversible and reversible mechanisms for inactivating the E-Cadherin-mediated cell adhesion system well correspond to the pathological features of human cancers.
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PMID:Molecular aspects of adhesion-epigenetic mechanisms for inactivation of the E-Cadherin-mediated cell adhesion system in cancers. 1121 45

The epidermal growth factor (EGF) receptor and its various ligands (EGF, TGF-alpha, amphiregulin, heparin-binding (HB)-EGF, heregulin, betacellulin) seem to be involved in the growth regulation of intestinal mucosa and might be related to the development and progression of gastrointestinal tumors. However, few quantitative data investigating the impact of tumor-EGF receptor levels in gastrointestinal carcinomas on tumor stage and prognosis are available. Therefore, EGF receptors were quantitatively determined in colorectal carcinomas in comparison to adjacent normal mucosa by 125I[EGF]-binding studies. EGFR capacity was increased in advanced invasive colorectal carcinomas (T1/2 vs. T3/4 tumors, p<0.001) and advanced UICC stages (UICC I vs. UICC II/III, p<0.001). These findings were confirmed with quantitative 125[I]EGF autoradiography performed on frozen tissue slides and analyzed by laser densitometry (p=0.020). EGF receptor analysis with immunohistochemistry with EGFR antibodies directed against the extracellular domain of the receptor was not correlated with tumor invasion or prognosis. mRNA-expression of EGFR ligands was investigated using semiquantitative RT-PCR amplification using specific primers. RT-PCR transcripts of EGFR ligands (EGF, TGF-alpha, HB-EGF, and amphiregulin) were detected in both carcinomas and normal mucosa, indicating that autocrine growth stimulation of colorectal carcinomas is mediated by coexpression of EGF receptor ligands and upregulation of EGF receptors. Survival of colorectal cancer patients with increased tumor EGF receptor levels was significantly reduced in comparison to patients with low/unchanged tumor EGF receptor levels (mean survival+/-SD, 36.2+/-4.0 vs. 46.8+/-4.3 months; p=0.017). Further studies investigating EGF receptor levels in gastric cancer patients have shown that increased tumor EGF receptor levels were associated with poor prognosis in gastric cancer patients with tumors localized distal from the cardia. Several specific EGF receptor tyrosine kinase inhibitors have recently entered clinical phase I-III studies, with promising antitumor effects in several tumors, including gastrointestinal cancer. Therefore, patients with invasive gastric or colorectal carcinomas might benefit from therapies specifically blocking EGFR-mediated signal transduction.
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PMID:Clinical implications of the EGF receptor/ligand system for tumor progression and survival in gastrointestinal carcinomas: evidence for new therapeutic options. 1279 Mar 26

The human epidermal growth factor (EGF) receptor (HER) family consists of four receptors that bind to ligands sharing an EGF-like motif. The HER family of receptor tyrosine kinases and their ligands (EGF family) are known to play a significant role in gastrointestinal cancer. In particular, the EGF receptor, HER1, is one of the main candidates for the molecular-targeted therapy of colon cancer, and HER2 is a candidate for the treatment of gastric cancer which overexpresses HER2. In contrast, the role of the HER and EGF families in malignant lymphoma has not been fully elucidated. In this study, we investigated the expression and function of the HER and EGF families in lymphoma cell lines and tumor samples. Reverse transcription polymerase chain reaction revealed that the ligands for HER1 were mainly expressed in gastric cancer and colon cancer cell lines, but not in lymphoma cell lines. On the other hand, the EGF family member, neuregulin (NRG) 4, was highly expressed in lymphoma cell lines. Immunohistochemical analyses of malignant lymphoma clinical samples revealed that NRG4 and HER4 were mainly expressed in mucosa-associated lymphoid tissue (MALT) and follicular lymphoma. Immunoprecipitation of Raji and Daudi cell lines revealed that recombinant NRG4 induced the tyrosine phosphorylation of HER4. Additionally, recombinant NRG4 activated the proliferation of lymphoma cell lines. These findings suggest that the NRG4-HER4 axis plays a major role in the proliferation of malignant lymphoma cells in the gastrointestinal tract.
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PMID:The role of neuregulin4 and HER4 in gastrointestinal malignant lymphoma. 2180 36