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 overexpression of p53, c-erbB-2 and p21ras gene products was evaluated immunohistochemically in ovarian carcinomas, borderline, and benign neoplasms. All studies were performed on cytospin preparations of cyst and/or ascitic fluid cells and mutual relations between oncoproteins were analysed. p53 and c-erbB-2 immunostaining was observed in 50% and 48.5% of ovarian carcinomas and in 30% and 35% of ovarian borderline tumors respectively, however in the last group the intensity and percentage of stained cells were considerably lower. In ovarian benign neoplasms there was no evidence of p53 and/or c-erbB-2 expression. The trend for serous carcinoma to have a higher p53 and c-erbB-2 expression than endometrioid and mucinous carcinomas was observed. p53 and c-erbB-2 oncoproteins were detected more frequently in the III/IV than in the I/II stages of the disease. The expression of p21ras was detected in 91% of malignant, 65% of borderline and 50% of benign neoplasms. p21ras reactivity was independent of the histopathological structure of ovarian carcinomas and it was comparable in I/II and III/IV FIGO stages. Our results indicate that p21ras overexpression appears to be an early genetic alteration in ovarian tumorigenesis, followed by the appearance of p53 and c-erbB-2 oncoproteins. It is likely that enhanced p53 and c-erbB-2 expression may cooperate with ras gene activation to produce a particularly aggressive phenotype. Our study supports the concept that development of ovarian carcinoma is the end result of a complex multistep process involving the complementary action of different cancer causing genes.
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PMID:p53, c-erbB-2 and p21ras expression in tumor effusion cells of patients with histopathologically different ovarian neoplasms. 941

Although the mechanism remains obscure, two histological subtypes of gastric carcinoma (GC), the diffuse and intestinal types, differ drastically in epidemiological, clinical, pathological and biological characteristics. We investigated whether the genetic alterations of several oncogenes and tumour suppressor genes could be correlated with the two histological subtypes. In 60 patients with GC, the overexpression of mutant p53 and c-erbB-2 oncoproteins was studied using immunohistochemical stains. Mutations of the p15 and p16 tumour suppressor genes were assessed by polymerase chain reaction, Southern blotting, and direct DNA sequencing. Overexpression of c-erbB-2 and p53 was found in 21 (35.0%) and 27 (45.0%) patients, respectively. Overexpression of the c-erbB-2 oncoprotein was more common in the intestinal type (15/32, 46.9%) and the advanced stage (19/45, 42.2%) than in the diffuse type (6/28, 21.4%) and the early stage (2/15, 13.3%) of GC (P<0.05). Similarly, p53 overexpression was more frequently found in the intestinal type (19/32, 59.4%) and the advanced stage (24/45, 53.3%) than in the diffuse type (8/28, 28.6%) and the early stage (3/15, 20.0%) of GC (P<0.05). Homozygous deletions of p16 in exon 1 were found in six (10.0%) patients. Five of them had the intestinal-type advanced GC. Neither point mutations of p16 nor alterations of p15 were detected. The frequency of alterations of p53, c-erbB-2, and p16 was not related to sex and Helicobacter pylori infection. No correlation of genetic changes between any two genes was observed. Our preliminary results indicate alterations in the p15 gene were not important in gastric tumorigenesis, while infrequent homozygous deletions in the p16 gene play a limited role in tumour progression of intestinal-type GC. Moreover, overexpression of c-erbB-2 and p53 is frequently encountered in the intestinal-type advanced GC. Alterations of p53, c-erbB-2 and p16 genes may function independently of each other in gastric carcinogenesis. The association between genetic alterations and histological subtypes supports the notion that a distinct pathogenesis may exist in different histological subtypes.
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PMID:Overexpression of mutant p53 and c-erbB-2 proteins and mutations of the p15 and p16 genes in human gastric carcinoma: with respect to histological subtypes and stages. 957 Feb 45

HER-2/neu oncogene is believed to be involved in tumorigenesis of several human malignancies. To assess the pattern of expression of this oncogene in normal, hyperplastic, and neoplastic endometrium, immunocytochemistry was applied to paraffin-embedded tissue sections obtained from 146 patients with endometrial adenocarcinoma. A spectrum of hyperplastic changes ranging from simple hyperplasia to atypical hyperplasia was seen in 15 percent (22/146) of cases. Expression for HER-2/neu oncogene was demonstrated as cell membrane staining. Normal, hyperplastic and neoplastic epithelial cells showed a heterogeneous expression for HER-2/neu oncogene. The intensity of the immunostaining and the number of cells stained for HER-2/neu oncogene had no significant association with surgical stage or histologic grade, although the proportion of patients demonstrating overexpression increased significantly as the histologic grade of their tumor increased (p = 0.030). Furthermore, in a multivariate analysis, a statistically significant correlation was found between the level of expression of HER-2/neu oncogene and overall survival (p = 0.025). This study demonstrated that HER-2/neu oncogene expression is variably present in normal and hyperplastic endometrium. Association between HER-2/neu oncogene expression, higher grade lesions and poor survival in patients with endometrial cancer may also justify assessment of HER-2/neu oncogene as a reliable prognostic indicator.
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PMID:Expression of HER-2/neu oncogene in normal, hyperplastic, and malignant endometrium. 964 53

The proto-oncogene bcl-2 is demonstrated to block a final common pathway leading to apoptosis and is expressed in more than half of human breast cancers. Invasive breast cancer has reduced bcl-2 immunostaining compared with normal breast epithelia and preinvasive breast lesions. As an inhibitor of apoptosis, bcl-2 should correlate with highly aggressive tumor biology and resistance to hormonal/cytotoxic therapy. However, high bcl-2 expression has been shown to associate with a number of favorable prognostic factors including ER positivity, PgR positivity, low histological grade, well-differentiated tumor, absence of c-erbB-2 and p53. Unexpectedly, numerous studies have shown that tumors with high bcl-2 expression are more responsive to hormone therapy and have more favorable disease-free and overall survival. The clinical significance of bcl-2 in tumorigenesis and prognosis of breast carcinomas from the data recently published are reviewed. Its role in modulation of hormonal/cytotoxic therapy and future directions are also discussed.
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PMID:The role of bcl-2 expression in breast carcinomas (Review). 968 37

Hereditary ovarian cancers associated with germline mutations in either BRCA1 or BRCA2 were studied to determine whether somatic mutation of the P53 gene is required for BRCA-linked ovarian tumorigenesis and further, whether the spectrum of additional somatic molecular genetic alterations present in these tumors differs from that known to exist in sporadic ovarian cancers. Forty tumors, 29 linked to BRCA1 and 11 linked to BRCA2, were examined for mutational alterations in P53, K-RAS, ERBB-2, C-MYC, and AKT2. The presence of a P53 mutation in 80% of these cancers indicates that P53 mutation is common but not required for BRCA-linked ovarian tumorigenesis; notably, a significantly higher proportion of the P53 mutations in BRCA2-linked cancers were deletions or insertions compared with the more typical spectrum of missense mutations seen in BRCA1-linked cancers. Additionally, BRCA-linked ovarian carcinomas seem to develop through a unique pathway of tumorigenesis that does not involve mutation of K-RAS or amplification of ERBB-2, C-MYC, or AKT2.
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PMID:Molecular genetic characterization of BRCA1- and BRCA2-linked hereditary ovarian cancers. 969 40

The overexpression of two growth factor receptors - epidermal growth factor receptor (EGFR) and c-erbB-2 - was evaluated immunohistochemically in malignant and benign ovarian neoplasms, considering the stage of the disease and histology of tumors. The comparison of EGFR and c-erbB-2 reactivity in tissue sections and respective cyst and/or ascitic fluid cells was also performed. c-erbB-2 expression was detected in 44.4% of ovarian carcinomas, and in benign neoplasms there was no evidence of its staining, while EGFR reactivity was found both in malignant (58.7%) and benign (50%) tumors. Significant heterogeneity of staining was observed, however, the relationship between EGFR and c-erbB-2 expression in tissue sections and cyst and/or ascitic fluid cells in individual patients was evident. The expression of both growth factor receptors was not correlated with histopathological subtypes of ovarian neoplasms. The c-erbB-2 oncoprotein was detected more frequently in III/IV than in I/II stages according to the criteria of the International Federation of Gynecology and Obstetrics (FIGO) and the EGFR expression was independent of the clinical advancement of the disease. The coexpression of c-erbB-2 and EGFR was shown in 32% of ovarian carcinomas, and it dominated in cases with FIGO stages III/IV. Our results indicate that the increase of the EGFR expression appears to be associated with early stages of ovarian tumorigenesis, and the enhancement of c-erbB-2 reactivity may cooperate with EGFR activation in the development and progression of ovarian carcinomas.
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PMID:Epidermal growth factor receptor and c-erbB-2 oncoproteins in tissue and tumor effusion cells of histopathologically different ovarian neoplasms. 970 27

The expression and coexpression of EGFR, c-erbB-2 and c-erbB-3 in 21 gastric cancers and 20 chronic gastritis was examined using immunohistochemistry on fresh frozen tissues considering clinicopathological variables. Generally, gastric cancer patients showed a higher incidence of EGFR, c-erbB-2 and d-erbB-3 overexpression than the group with chronic gastritis (81% and 43%; 38% and 45%; 35% and 20%, respectively), however, statistically significant differences were found only for EGFR expression (p = 0.01). No association between immunoreactivity of all growth factor receptors and the histopathological structure of gastric cancer was observed. EGFR and c-erbB-3 proteins were detected more frequently in patients with III/IV than in I/II of TNM stages, while c-erbB-2 overexpression was higher in I/II vs. III/IV stages. In chronic gastritis with intestinal metaplasia and or coexisting carcinoma lesions, a higher frequency of the expression of studied proteins was observed in comparison with chronic gastritis without those alternations; however, these differences were statistically insignificant. The percentage of positive cases with coexpression of two proteins was comparable in gastric cancer and chronic gastritis (33% and 35%) but the simultaneous expression of all three receptors was evident only in gastric cancer (19%). Our results indicate that at least one or two members of EGFR related receptors could appear in the early stages of gastric tumorigenesis. The enhancement of c-erbB-2 and c-erbB-3 reactivity seems to cooperate with EGFR activation in the gastric cancer development. Our results indicate the promotional rather than direct transformational role for EGFR supergene family in gastric carcinogenesis.
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PMID:Expression of epidermal growth factor receptor family proteins (EGFR, c-erbB-2 and c-erbB-3) in gastric cancer and chronic gastritis. 970 36

Overexpression of p185erbB2/neu has been demonstrated in approximately 30% of prostatic carcinomas and has been shown to induce tumorigenesis and metastasis in a prostatic epithelial cell line, NbE. To metastasize successfully, cells must be able to proliferate, degrade and be motile on a variety of substrates; thus attachment and spreading on a variety of substrates are key features of the metastatic phenotype. Using in vitro assays, we demonstrate that NbE-neuT-9/10 clones attached significantly better to specific substrates and spread significantly better on both specific and non-specific substrates as compared to the control clones. Additionally, the expression of integrin alpha6beta1, a key receptor enabling attachment and spreading on laminin, is upregulated on the metastatic clones NbE-neuT-9 and 10.
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PMID:Overexpression of p185erbB2/neu in the NbE prostatic epithelial cell line increases cellular spreading and the expression of integrin alpha6beta1. 982 30

The ErbB-2 receptor has been strongly implicated in the development of breast cancer. To establish a new model system to investigate the role of erbB-2 in tumorigenesis of the breast, the conditionally immortalised human mammary luminal epithelial cell line HB4a was transfected with erbB-2 cDNA. Biological and biochemical characterisation of the resulting cell lines demonstrated that high levels of ErbB-2 expression were sufficient to cause transformation in vitro but did not cause tumours in vivo. Transformation by overexpression of ErbB-2 correlated with ligand-independent tyrosine phosphorylation of ErbB-2 and the adaptor protein Shc. Over-expression of ErbB-2 also resulted in the ligand-independent constitutive association between Shc and another adaptor protein, Grb2, indicating that receptor activation was sufficient to activate downstream signalling pathways. Using the model described, it was found that elevation of ErbB-2 expression levels caused marked quantitative and qualitative alterations in responses to the ligands epidermal growth factor and heregulin. Data indicate a central role for ErbB-2 in mediating the responses induced by these ligands and suggest that these altered ligand-dependent responses play an important role in tumorigenesis in vivo.
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PMID:New model of ErbB-2 over-expression in human mammary luminal epithelial cells. 993 93

The pathobiology of precursor lesions leading to invasive pancreatic adenocarcinoma remains a controversial area, but knowledge of the mechanisms of tumorigenesis may lead to possibly earlier detection, prevention, and treatment in the future. We hypothesize that ductal hyperplasia and dysplasia of the pancreas represent precursor lesions and are part of a continuous developmental spectrum evolving into ductal adenocarcinoma of the pancreas. To further define this sequence, we studied the immunohistochemical markers HER-2/neu, K-ras, and p53 in 15 adenocarcinomas and 15 nonmalignant specimens of the pancreas. The 15 nonmalignant specimens of the pancreas included both normal pancreas and chronic pancreatitis. Overall, HER-2/neu was positive in normal ducts, ductal hyperplasia, dysplasia, and carcinoma cells in 0 of 30, 11 of 20 (55%), 10 of 15 (67%), and 12 of 15 (80%), respectively, with progressive increase in the intensity of staining; p53 was positive in 1 of 30 (3%), 0 of 20, 3 of 15 (20%), and 13 of 15 (80%), respectively, and K-ras was positive in 1 of 30 (3%), 6 of 20 (30%), 11 of 15 (73%), and 8 of 15% (53%), respectively. These data support the hypothesis that ductal hyperplasia and dysplasia of the pancreas represent precursor lesions, and, in a fashion similar to that in colorectal tumorigenesis, pancreatic cancer seems to accumulate progressive genetic alterations.
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PMID:Immunohistochemical evaluation of K-ras, p53, and HER-2/neu expression in hyperplastic, dysplastic, and carcinomatous lesions of the pancreas: evidence for multistep carcinogenesis. 1002 38


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