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)

Expression of four biologic markers was studied in 69 cases of endometrial cancer to identify their association with cell type, decreased survival, and increased tumor metastasis. Cell types included endometrioid (n = 45), serous papillary (n = 16), and clear cell (n = 8). Immunohistochemical stains were employed to detect the presence of epidermal growth factor receptor (EGFR), HER-2/neu, p53, and proliferating cell nuclear antigen (PCNA). Analysis revealed that EGFR was expressed in 49%, HER-2/neu in 59%, p53 in 9%, and PCNA in 16% of tumor specimens. HER-2/neu overexpression was significantly associated with depth of myometrial invasion. p53 and PCNA immunoreactivity significantly correlated with nonendometrioid histology, although PCNA was less specific in labeling these less favorable cell types. EGFR immunoreactivity also significantly correlated with nonendometrioid cell types and tumor metastases at time of diagnosis. Seventy-seven percent of patients with metastatic disease were EGFR-positive versus 36% positivity in patients with no evidence of metastases (P < 0.002). For patients with endometrioid adenocarcinoma, evidence of EGFR overexpression decreased survival from 89 to 69% (P < 0.04). In the serous papillary and clear cell category, EGFR positivity decreased survival from 86 to 27% (P < 0.03). EGFR strongly correlates with tumor metastasis and patient survival in endometrial cancer. Altered expression of this oncoprotein may serve as a guide to prognosis and treatment in these patients.
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PMID:Expression of EGFR, HER-2/neu, P53, and PCNA in endometrioid, serous papillary, and clear cell endometrial adenocarcinomas. 790 88

The new monoclonal antibodies (MoAbs) E401, E811, E907 and E919 were prepared and characterized. These recognized an extracellular domain (amino acids No. 292-370) on the human c-erbB-2 gene product. Utilizing MoAb E811 and MoAb E919, a double determinant immunoassay (DDIA) was established to detect the soluble and the shed forms of the c-erbB-2 molecule. The levels of circulating erbB-2 antigen in the sera of patients with benign diseases and healthy controls were very low. The incidence of positivity for shed c-erbB-2 antigen in gastric cancer, colonic cancer, gall-bladder cancer, pancreatic cancer and other cancers were 7.4%, 4.2%, 0%, 6.7% and 0%, respectively. Four of 54 patients with gastric carcinoma showed high levels of serum c-erbB-2 antigen. They belonged to clinical stage IV and their histological types were all well differentiated adenocarcinomas (two papillary and two tubular adenocarcinomas). Furthermore, the incidence of positive staining in gastric cancer was 34.6%; higher than that for shedding erbB-2 antigen. Most of the cases which showed erbB-2 expression on cells were well-differentiated adenocarcinomas. Meanwhile, the distribution of erbB-2 antigen was limited in normal tissues. The results suggest that the expression of erbB-2 antigen is largely restricted to adenocarcinoma cells. It may not shed easily from these cells, and therefore it may be a very useful target molecule for passive immunotherapy.
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PMID:Significance of erbB-2 gene product as a target molecule for cancer therapy. 791 Jul 4

A series of benzylidenemalononitrile derivatives previously synthesized by condensing aromatic aldehydes with malononitrile derivatives are known as tyrphostins. In this study, 32 tyrphostins were synthesized, 19 of which are novel compounds. Both hydroxylated derivatives and compounds containing heteroaromatic moieties were prepared. We have confirmed and extended the observation that the tyrphostins displayed an enhancement in their ability to inhibit the epidermal growth factor (EGF) receptor tyrosine kinase domain as the number of hydroxyl groups on the aromatic portion was increased. IC50 values of 1-5 microM were readily achieved. Some inhibitory activity was seen with the heteroaromatic structures, with two compounds exhibiting IC50 values of 56 and 77 microM. However, these derivatives were poor inhibitors of the EGF receptor tyrosine kinase activity as compared to the hydroxylated derivatives. The ability of the 32 tyrphostins synthesized in the present study to inhibit proliferation of a human breast adenocarcinoma cell line (MCF-7) was determined using [3H]thymidine incorporation as a measure of DNA synthesis. Some of the compounds containing pyridine, imidazole or thiophene portions displayed antiproliferative activity comparable to that of tyrphostins prepared from 3,4,5-trihydroxybenzaldehyde. The lack of inhibitory effect of these heteroaromatic compounds on the EGF receptor tyrosine kinase activity suggests that their antiproliferative activity is not related to inhibition of EGF receptor function. As the growth of the MCF-7 cell line is governed by other factors, such as the insulin-like growth factors (IGFs) and oestradiol, it is also still to be established whether the antiproliferative activity of the hydroxylated tyrphostins is directly related to inhibition of the EGF receptor tyrosine kinase activity.
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PMID:Synthesis and antiproliferative activity of tyrphostins containing heteroaromatic moieties. 791 98

The epidermal growth factor receptor (EGFR) is structurally similar to the c-erbB-2 oncogene protein. One hundred and nineteen specimens of primary human lung adenocarcinoma were investigated immunohistochemically for the expression of EGFR and the c-erbB-2 protein. Positive staining for EGFR was evident in 55 (46%), and c-erbB-2 protein in 33 (28%) cases. Of the 119 cases, the number staining positively for both the EGFR and c-erbB-2 protein totalled 16 (13%). The incidence of both the expression of EGFR and the c-erbB-2 protein was greater in patients with metastasis1 (M1) than in those with M0 (P < 0.01). The 5-year survival rates of patients with EGFR positivity and those with EGFR negativity were 51% and 42% respectively, however, the results did not show statistical significance. On the other hand, the 5-year survival rates of patients with c-erbB-2 positivity and c-erbB-2 negativity were 30% and 52%, respectively, with statistical significance (P < 0.05). Of the cases with EGFR positivity the 5-year survival rates of patients with c-erbB-2 positivity (n = 16) and negativity (n = 39) were 33% and 59%, respectively, with statistical significance (P < 0.05). In contrast, for the EGFR negative cases, the 5-year survival rates of patients who were positive (n = 17) and negative (n = 47) for c-erbB-2 expression were 27% and 46%, respectively, which were not significantly different. Our data thus suggested that erbB oncogenes may play an important role in both the development of cancer and the prognosis of adenocarcinoma of the lung.
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PMID:Prognostic influence of the co-expression of epidermal growth factor receptor and c-erbB-2 protein in human lung adenocarcinoma. 795 90

The c-erbB-2 protooncogene has been shown to be overexpressed and/or amplified in carcinomas of the breast, ovary, pancreas, and other organs. Several studies of human breast carcinoma noted an association of c-erbB-2 overexpression and amplification with poor prognosis. Recent studies have demonstrated c-erbB-2 protein expression in a variety of salivary gland neoplasms, most notably pleomorphic adenoma (PA), carcinoma ex pleomorphic adenoma (CAexPA), and adenocarcinoma. In this study, we analyzed c-erbB-2 expression in 15 PAs and 13 CAexPAs, using immunohistochemistry. In addition, differential polymerase chain reaction was used to evaluate c-erbB-2 gene amplification in these tumors. Low-level c-erbB-2 immunoreactivity was detected in three of 15 PAs. Among the CAexPAs, low-, intermediate-, and high-level immunoreactivity was seen in two, three, and two cases, respectively. The only cases showing c-erbB-2 amplification were the two CAexPA cases with high-level immunoreactivity. Based on statistical analysis of the 10 CAexPA patients with known outcome, no significant association of prognosis with c-erbB-2 expression or amplification was apparent.
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PMID:c-erbB-2 oncoprotein expression and amplification in pleomorphic adenoma and carcinoma ex pleomorphic adenoma: relationship to prognosis. 799 21

Esophageal cancer is one of the 10 most prevalent human cancers worldwide. The incidence of esophageal adenocarcinoma is on the rise and patients with this disease typically have very poor prognosis. Informative biomarkers would benefit the clinical management of this disease. We examined 13 cases with esophageal adenocarcinomas and 5 cases with Barrett's esophagus for amplification of the EGFR and erbB-2 genes. We detected multiple copies of the EGFR gene in 30.8% of the tumors and multiple copies of the erbB-2 gene in 15.4% of the tumors. Of the cases with amplification of the erbB-2 gene, co-amplification of the EGFR gene was found. Multiple copies of the EGFR gene were also found in one case of Barrett's esophagus. Immunohistochemical staining of the tissues revealed increased expression of the erbB-2 protein in Barrett's mucosa and adenocarcinoma, but no associations between staining intensity and degree of EGFR or erbB-2 gene amplification, histology, or tumor stage were found. Differential polymerase chain reaction was examined as a method for pre-operative detection of gene amplification in esophageal tumors and Barrett's mucosa.
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PMID:Amplification and over-expression of the EGFR and erbB-2 genes in human esophageal adenocarcinomas. 809 13

The pathogenicity of the human c-erbB-2 oncogene was evaluated in transgenic mice. A DNA sequence comprising the promoter-enhancer region of the MMTV LTR and a constitutively activated allele of the human c-erbB-2 growth factor receptor gene was introduced into the germ line of mice. Expression of the transgene was observed in kidney, lung, mammary gland, salivary gland, Harderian gland, and in epithelial cells of the male reproductive tract. All transgenic mice expressing the c-erbB-2 receptor died within four months of birth. Histopathological analysis suggests that preneoplastic lesions in kidney and lung most likely caused organ failure and the early death of the transgenic mice. Focal dilatation and atypical proliferation of the tubular epithelial cells was found in the kidney. These hyperplastic lesions were found adjacent to normal tubules. Immunohistochemistry showed that normal renal structures were completely negative for c-erbB-2 protein expression. Atypical pseudopapillary proliferation of bronchial and bronchiolar epithelial cells narrowed the bronchial lumen in lung. Alveoli appeared normal. The expression of c-erbB-2 protein was strictly limited to the proliferating epithelial cells and not detected in normal tissue. The mammary glands of two parous mice were underdeveloped, lacking lobular-alveolar structures and were lactation deficient. Only a few ducts were interspersed in the fat pad. A virgin mouse developed a focal adenocarcinoma infiltrating the mammary fat pad. Expression of the c-erbB-2 protein was enhanced in the proliferating epithelial cells. Transgenic males were sterile. Epithelial hyperplasia and hypertrophy in the epididymis, vas deferens and seminal vesicles was found. The transgene is not uniformly expressed in the tissues where the MMTV LTR is transcriptionally active. The scattered transgene expression invariably coincides with epithelial hyperplasia.
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PMID:An activated allele of the c-erbB-2 oncogene impairs kidney and lung function and causes early death of transgenic mice. 810 Feb 31

Proto-oncogenes represent a family of normal cellular genes that were identified on the basis of their similarity to genetic sequences with known tumorigenic or transforming potential. Accumulating evidence links alterations in either the structure, copy number, or expression of one or another of these genes to neoplasia. One such gene, called erbB-2/Her-2 was found amplified in an adenocarcinoma of the human salivary gland and has also been found associated with primary human breast cancer. Patients with multiple copies of the gene have had a shorter overall survival. In the present study, 21 tumors of the parotid gland were examined by Southern and Northern blot hybridization for amplification and possible overexpression of the erbB-2/Her-2 oncogene. Normal parotid gland tissue was used as negative control. The parotid gland lesions comprised 7 pleomorphic adenomas, 5 squamous cell carcinomas, 4 cases of chronic fibrotic sialadenosis, 3 mucoepidermoid carcinomas as well as 1 lymphoma and 1 cystadenolymphoma. Gene amplification was found in 1 of the pleomorphic adenomas, with 2 tumors showing a significant overexpression of the erbB-2/Her-2 oncogene. Because 3-5% of all pleomorphic adenomas undergo malignant transformation, close follow-up of patients is currently underway.
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PMID:erbB-2/Her-2 gene amplification and overexpression in parotid gland tumors. 810 55

Endometrial cancers have been considered to be less prevalent in Japan than in Western countries. However, with the increase in life expectancy, the Westernization of the Japanese diet, and changes in the hormonal environment, the prevalence of the disease has gradually increased even in our country. Similar increases in cancers of the breasts, lungs, colons, and ovaries have been noted in recent years. Much is still unknown regarding the pathogenesis and natural history of endometrial cancer. Although endometrial hyperplasia is considered to be a precancerous lesion of endometrial carcinoma, the relationship between those diseases has not been elucidated to the same degree as that between cervical cancer and cervical dysplasia, or carcinoma in situ. Research findings in genetic oncology have revealed that tumorigenesis involves a multi-step process. It is probable that activation of multiple genes, inactivation of anti-oncogenes, and disappearance of normal inhibitor genes occur in the process of the development of endometrial cancer. The purpose of this study is to elucidate the relationship between oncogenes and the development of endometrial cancer. In addition, the significance of endometrial hyperplasia as a clinical entity is also be evaluated. The roles played by oncogenes in endometrial cancers and endometrial hyperplasias were examined using the most recent molecular biological and immunohistochemical methods. Also, the differences in cellular proliferation and tissue invasiveness were discussed. Results obtained were as follows. Evaluation of cell proliferation (PCNA, FCM) revealed that there was no difference in proliferative activity between atypical hyperplasia and well differentiated adenocarcinoma. Evaluation of oncogene abnormalities (c-myc,c-erbB-2,K-ras,p53) revealed that the development of endometrial cancer was a multistep process involving several oncogenes, as it has been noted in the development of other cancers. Evaluation of extracellular matrix and related factors (cathepsin D, laminin, type IV collagen, tenascin, CD44) showed that tissue invasiveness differed between atypical hyperplasia and well differentiated adenocarcinoma.
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PMID:[Evaluation of the degree of biological behavior in endometrial hyperplasia and endometrial carcinoma: an investigation of proliferative activity, oncogene, and extracellular matrix]. 810 84

Acquired cystic disease of the kidney (ACDK) reveals abnormal epithelial cell growth which suggests a cotinuum of cyst, adenoma and renal cell carcinoma (RCC). In the present study, we examined potential role of vimentin and growth factors for cyst growth and proliferation in 20 cases with ACDK by immunoperoxidase staining method. 1281 cysts with single-layered epithelia and 89 cysts with multi-layered epithelia (atypical cyst) were studied. Intermediated filament, vimentin was positive in staining in 41.6% of cysts with single-layered epithelia, in 73.1% of cyst with multi-layered epithelia and in 100% of adenomas and RCCs. Vimentin expression, therefore, may be considered as an indication of cellular differentiation among proliferating tubular or intracystic cells. In order to evaluate the growth and/or proliferative capabilities of cyst epithelia, epidermal growth factor (EGF), epidermal growth factor receptor (EGFR) and c-erb B2 gene product were determined in cyst epithelia, adenoma and adenocarcinoma. EGF showed positive staining in 49.1% of cyst with single-layered epithelia, in 68.4% of cyst with multi-layered epithelia, in 2 of 3 adenomas and in 5 of 8 RCCs. EGFR expression was observed in 61.7% of cyst with single-layered epithelia, in 94.7% of cyst with multi-layered epithelia, in 100% of adenomas and RCCs. Co-expression of EGF and EGFR was observed in 40.3% of cyst with single-layered epithelia and in 67.1% of cyst with multi-layered epithelia. C-erb B2 gene product was positive in 9.7% of cyst with single-layered epithelia, in 100% of cyst with multi-layered epithelia and in 3 of 7 RCCs. These findings indicate that the expression of vimentin and overexpression of these growth factors and receptors appear to be one of the mechanisms operating in potentiating the abnormal growth of cyst epithelia, including potential for oncogenesis of RCC.
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PMID:[Immunohistochemical study in acquired cystic disease of the kidney--expression of vimentin, epidermal growth factor, epidermal growth factor receptor and c-erb B2 gene product]. 810 22


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