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)

The immunohistochemical detection of the c-erbB-2 oncopeptide (p185erbB2) has been shown to be a valid marker for over-expression of this oncogene. To evaluate the possible relevance of gene expression to the proliferation of hepatocytes and bile ducts in human disease, the authors applied a monoclonal anti-p185 antibody to formalin-fixed, paraffin-embedded tissues from 67 examples of benign proliferative and neoplastic hepatic lesions and fetal liver. Focal membrane-based reactivity for the oncopeptide was detected on tumor cells in two of eight hepatocellular carcinomas and on tumor cells and adjacent bile ducts and hepatocytes in four of six cholangiocarcinomas. Each of the latter four lesions were in patients with primary sclerosing cholangitis. No reactivity was obtained in examples of hepatoblastoma, mixed cholangiocarcinoma-hepatocellular carcinoma, bile duct adenoma, or hepatocellular adenoma. Weak staining for p185erbB2 also was seen in two of seven cases of (sub)massive hepatic necrosis and two examples of postnecrotic cirrhosis, all of which were secondary to either hepatitis B or C virus infection. No other benign proliferative lesions were labeled by the anti-p185 antibody, including cases of chronic allograft rejection, necrosis secondary to hepatic artery thrombosis, metabolic-associated and nonmetabolic-associated cirrhosis, focal nodular hyperplasia, and nodular regenerative hyperplasia. The authors' results indicate that c-erbB-2 may be amplified in specific neoplastic and hepatitis B virus and hepatitis C virus infectious lesions of liver. The authors postulate that: (1) c-erbB-2 immunoreactivity may be a marker for malignant transformation in primary sclerosing cholangitis; and 2) overproduction of p185erbB2 may be an epiphenomenon of hepatitis B virus or hepatitis C virus infection.
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PMID:Immunoreactivity for c-erbB-2 oncopeptide in benign and malignant diseases of the liver. 137 19

AIM:To study hepatocarcinogenesis of hepatitis C virus (HCV).METHODS: Expression of HCV antigens (CP10, NS3 and NS5) and several cancer-associated gene products (ras p21, c-myc, c-erbB-2, mutated p53 and p16 protein) in the tissues of hepatocellular carcinoma (HCC, n = 46) and its surrounding liver tissue were studied by the ABC(avidin-biotin complex) immunohistochemical method. The effect of HCV infection on expression of those gene products in HCC was analyzed by comparing HCV antigen positive group with HCV antigen negative group.RESULTS:Positive immunostaining with one, two or three HCV antigens was found in 20 (43.5%) cases,with either of two or three HCV antigens in 16 (34.8%) cases, and with three HCV antigens in 9 (19.6%) cases.Deletion rate of p16 protein expression in HCC with positive HCV antigen (80%, 16/20)was significantly higher than that in HCC with negative HCV antigen. Whereas no significant difference of the other gene product expression was observed between the two groups.CONCLUSION:HCV appears related to about one third of cases of HCC in Chongqing, the southwest of China, and it may be involved in hepatocarcinogenesis by inhibi ting the function of p16 gene, which acts as a negative regulator of cell cycle.
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PMID:Effect of HCV infection on expression of several cancer-associated gene products in HCC. 1181 78

Transforming growth factor beta (TGF-beta), a pro-fibrogenic cytokine, has several polymorphism in humans with difference in activity levels. Hepato-carcinogenesis involves alterations in the action of protooncogenes such as the; neu (C-erb-B2) oncogene. Overexpression of the neu-oncogene has been implicated in experimental cellular transformation and tumorigenesis in a wide range of human cancer. We examined TGF-beta1 and C-erb-B2 mRNA expression and their protein levels in hepatitis C virus (HCV) patients and those developing Hepatocellular carcinoma (HCC). Sixty patients (30 HCV and 30 HCC) and 30 controls were enrolled. HCV patients were classified into mild, moderate, marked and no fibrosis. HCC patients were categorized into grade I, II, Ill. TGP-beta1 and C-erb-B2 expression were studied. Messenger RNA was extracted using the guanidinum thiocyanate phenol chloroform method, and used of RT-PCR. Protein serum levels were estimated by (EIA). Significant difference were obtained when comparing TGF-bet1 and C-erb-B2 mRNA in HCV and HCC P = 0.0076, and controls. The HCV group revealed significant difference with C-erb-B2 but not TGF-B1 mRNA as compared to controls P < 0.005 and P > 0.05 respectively. Serum protein levels demonstrated difference increase significance shown when comparing their levels in both studied groups P < 0.001, P < 0.05 respectively and when compared to controls (P < 0.001). TGF-beta1 serum levels in HCV patients showed increase with degree of fibrosis (P = 0.003) while, C-erbB-2 serum levels showed no significance (P = 0.089). In different grades of HCC patients, TGF-beta1 levels showed no significant difference (P = 0.769). However, C-erb-B2 levels revealed significant difference (P = 0.002) between grade I & III and grade II &. Ill (P < 0.001). Positive correlations to protein serum level were obtained with TGF beta1mRNA in HCV group, while, C-erb-B2 mRNA in HCC patients. In conclusion, TGF-beta1 upregulation in HCC suggests its role in hepatic carcinogenesis. Elevated expression of C-erb-B2 may reflect pre-neoplastic liver cell proliferation, cellular necrosis associated with chronic liver disease and alternatively from HCV carcinogens which enhance malignant transformation. Correlation of both parameters with their protein levels might rise using their antibodies in immunotherapy for HCC.
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PMID:TGF-beta1 and C-erb-B2 neu oncoprotein in Egyptian HCV related chronic liver disease and hepatocellular carcinoma patients. 2030 68

Amphiregulin (AREG) is a ligand of the epidermal growth factor (EGF) receptor and may play a role in the development of cirrhosis and hepatocellular carcinoma in patients infected with hepatitis C virus (HCV). AREG showed an enhanced expression in HCV-infected human hepatoma cells according to gene array analysis. Therefore, we addressed the question about the role of AREG in HCV infection. AREG expression level was elevated in hepatoma cells containing a subgenomic HCV replicon or infected by HCV. Using a reporter assay, AREG promoter activity was found to be upregulated upon HCV infection. The enhanced AREG expression in hepatoma cells was partly caused by dsRNAs, HCV NS3 protein and autocrine stimulation. AREG was able to activate cellular signalling pathways including ERK, Akt and p38, promote cell proliferation, and protect cells from HCV-induced cell death. Further, knockdown of AREG expression increased the efficiency of HCV entry, as proven by HCV pseudoparticles reporter assay. However, the formation and release of infectious HCV particles were reduced by AREG silencing with a concomitant accumulation of intracellular HCV RNA pool, indicating that the assembly and release of HCV progeny may require AREG expression. Blocking the MAPK-ERK pathway by U0126 in Huh7.5.1 cells had a similar effect on HCV replication. In conclusion, HCV infection leads to an increase in AREG expression in hepatocytes. AREG expression is essential for efficient HCV assembly and virion release. Due to the activation of the cellular survival pathways, AREG may counteract HCV-induced apoptosis of infected hepatocytes and facilitate the development of liver cirrhosis and hepatocellular carcinoma.
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PMID:Hepatitis C virus infection induces the expression of amphiregulin, a factor related to the activation of cellular survival pathways and required for efficient viral assembly. 2165 55

Hepatitis C virus (HCV) establishes a persistent infection that in many cases leads to cirrhosis and hepatocellular carcinoma. The non-structural 5A protein (NS5A) has been implicated in this process as it contains a C-terminal polyproline motif (termed P2) that binds to Src homology 3 (SH3) domains to regulate cellular signalling and trafficking pathways. We have shown previously that NS5A impaired epidermal growth factor (EGF) receptor (EGFR) endocytosis, thereby inhibiting EGF-stimulated EGFR degradation by a mechanism that remained unclear. As EGFR has been implicated in HCV cell entry and trafficking of the receptor involves several SH3-domain containing proteins, we investigated in more detail the mechanisms by which NS5A perturbs EGFR trafficking. We demonstrated that the P2 motif was required for the NS5A-mediated disruption to EGFR trafficking. We further demonstrated that the P2 motif was required for an interaction between NS5A and CMS, a homologue of CIN85 that has previously been implicated in EGFR endocytosis. We provided evidence that CMS was involved in the NS5A-mediated perturbation of EGFR trafficking. We also showed that NS5A effected a loss of EGFR ubiquitination in a P2-motif-dependent fashion. These data provide clues to the mechanism by which NS5A regulates the trafficking of a key cellular receptor and demonstrate for the first time the ability of NS5A to regulate host cell ubiquitination pathways.
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PMID:Hepatitis C virus NS5A protein blocks epidermal growth factor receptor degradation via a proline motif- dependent interaction. 2587 41