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)

We examined samples of tumors of human breast, ovary, and colon of various degrees of malignancy for the expression of p53 protein, using a panel of anti-p53 antibodies and peroxidase immunohistochemistry. Of 66 tumor cases (24 cases of ovarian carcinoma, 23 cases of colon adenocarcinoma, and 19 cases of breast carcinoma), 36 (53%) showed high levels of expression of p53 using a human-specific antibody, and 16 (24%) showed high expression of a mutant form of p53. In the mutant p53-positive breast tumor samples, six (86%) were positive for HER-2/neu reactivity, compared with colon (0/4) and ovarian tumors (1/5). The pattern of p53 intracellular localization and tissue distribution, and the relationship between the expression of mutant p53 and cell differentiation, were also examined; poorly differentiated cells showed either overexpression of p53 or higher levels of mutant p53 in comparison with more normal cells.
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PMID:Immunohistochemical analysis of p53 and HER-2/neu proteins in human tumors. 168 Aug 97

203 primary human lung tumours, of which 119 were adenocarcinoma and 84 were squamous cell carcinoma, were investigated immunohistochemically for the expression of c-erbB-2 protein. Positive staining was evident in 33 (28%) of adenocarcinomas and 2 (2%) of squamous cell carcinomas. In cases of adenocarcinoma, c-erbB-2 was present in 18% of those with stage I disease. In stage IIIA, stage IIIB and stage IV cases, c-erbB-2 was present in 39%, 50% and 60%, respectively (I vs. IIIA and I vs. IIIB: P less than 0.05, I vs. IV: P less than 0.01). The 5-year survival rates of c-erbB-2 positive patients and those who were negative were 30% and 52%, respectively, with a statistically significant difference (P less than 0.01). These observations suggest that when the expression of c-erbB-2 correlates with invasiveness of the tumour, this correlation may serve as a prognostic indicator, particularly in cases of adenocarcinoma of the lung.
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PMID:Prognostic value of c-erbB-2 protein expression in human lung adenocarcinoma and squamous cell carcinoma. 168 76

The overexpression of the c-erbB-2 oncoprotein is now thought by most authors to be associated with adverse prognosis in breast carcinoma. In this study, we investigate the relationship between overexpression of the c-erbB-2 oncoprotein and nuclear size by morphometry in a series of 150 human breast carcinomas, comprising 65 cases of ductal carcinoma in situ (DCIS) and 85 cases of invasive adenocarcinoma. The mean nuclear size for c-erbB-2 positive cases of DCIS was 54.8 micron 2 and invasive carcinoma was 52.1 micron 2 respectively, in contrast with 41.6 micron 2 and 42.5 micron 2 for c-erbB-2 negative cases of DCIS and invasive carcinoma respectively. Flow cytometric examination of DNA in a subset of 91 of these tumours showed no association between tumour cell aneuploidy and c-erbB-2 overexpression. S-phase fraction could be calculated on 20 cases of DCIS and 48 invasive carcinomas. There was a strong association between c-erbB-2 overexpression, S-phase fraction (p less than 0.001) and proliferative index (p less than 0.001) in 20 cases of DCIS. A weak association of S-phase fraction and c-erbB-2 overexpression was seen in 48 invasive carcinomas (p = 0.047). This study confirms the subjective impression that there is a relationship between large tumour cell nuclear size and an overexpression of the c-erbB-2 oncoprotein, and also shows an association with increased tumour cell proliferation.
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PMID:Nuclear and flow cytometric characteristics associated with overexpression of the c-erbB-2 oncoprotein in breast carcinoma. 168 5

Primary and metastatic tumor tissues of serous papillary adenocarcinoma of the endometrium were examined for the following: (1) amplification of int-2, c-erbB-2 and c-myc proto-oncogenes by Southern blot hybridization; (2) DNA ploidy by flow cytometric study; (3) and expression of specific proteins, such as estrogen and progesterone receptors, keratin, vimentin, and carcinoembryonic antigen (CEA) using immunohistochemical and biochemical techniques. Amplification of c-myc was observed in the specimens from the endometrium (ten-fold) and from omental metastasis (five-fold). Both int-2 and c-erbB-2 amplification were not observed. The tumor showed aneuploidy, with the specimens from the endometrium and omental metastasis exhibiting multiple populations of aneuploid tumor cells. Estrogen and progesterone receptors could not be detected biochemically; however, immunohistochemically, estrogen receptors were observed in tumor cells forming papillary structures but not in the tumor cells of the solid, more poorly differentiated areas. A similar distribution was observed for both low and high molecular weight keratin. The findings of c-myc amplification and aneuploidy in the serous papillary adenocarcinoma of the endometrium are consistent with its aggressive behavior observed clinically and emphasize the importance of distinguishing this lesion from other types of endometrial carcinoma.
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PMID:Serous papillary adenocarcinoma of the endometrium. Analysis of proto-oncogene amplification, flow cytometry, estrogen and progesterone receptors, and immunohistochemistry. 169 76

Formalin-fixed, paraffin-embedded tissue sections from 45 patients with mammary and extramammary Paget's disease were stained immunohistochemically with the use of a polyclonal antiserum directed against a 14-amino acid segment of the c-erbB-2 oncoprotein. Positive membrane staining, which correlates with gene amplification, was found in 15 of 19 cases (79%) of mammary Paget's disease, 4 of 13 cases (31%) of vulvar Paget's disease, none of 8 cases of scrotal Paget's disease, and none of 5 cases of perianal Paget's disease. Of the 19 patients with mammary Paget's disease, specimens of underlying breast tissue were available from 14; all contained a concurrent ductal adenocarcinoma. Concordance of c-erbB-2 antigen staining between the underlying breast carcinoma and the pagetoid component was observed in 12 cases. Of the 13 patients with vulvar Paget's disease, 2 had superficial stromal invasion, and 3 had underlying, deeply invasive adenocarcinomas. One superficially invasive case was positive for c-erbB-2 expression. One additional case of vulvar Paget's disease had an associated primary pagetoid endocervical adenocarcinoma that spread into the endometrium; both the endocervical and vulvar components stained positively for the c-erbB-2 antigen. The results of this study indicate that the c-erbB-2 oncoprotein may play a role in the pathogenesis of extramammary Paget's disease. These results also suggest that the c-erbB-2 oncoprotein may function in vivo to promote intraepithelial spread of adenocarcinoma cells.
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PMID:Expression of c-erbB-2 oncoprotein in mammary and extramammary Paget's disease. 171 41

Esophageal and gastric cancers are highly virulent tumors with an especially poor prognosis. They are rather common tumors in the United States with an anticipated annual incidence of approximately 32,000 new patients in 1991. Adenocarcinomas of the proximal stomach and lower esophagus are rapidly increasing in incidence; the reasons for this remain unclear. Endoscopic ultrasonography has offered a new dimension to staging especially of the primary tumor but also shows promise for more accurate identification of nodal metastasis. While stage remains the single most important prognostic variable, biological studies investigating tumor markers are a high priority; aneuploidy and HER-2/neu amplification or overexpression may predict poor outcome in gastric cancer. Esophageal and gastric cancers have a high local and distant failure rate when treated with conventional therapy. New developments in chemotherapy in the neoadjuvant and postoperative setting are under intense investigation in an attempt to improve prognosis for these diseases.
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PMID:Therapy of upper gastrointestinal tract cancers. 174 44

The c-erbB-2 proto-oncogene is known to encode a 185,000 molecular weight glycoprotein. This protein has been detected immunohistochemically in several human adenocarcinomas, suggesting that it may play a role in the development of these malignancies. In the otolaryngological field none of the adenocarcinomas expressing c-erbB-2 protein has yet been described. In this article we presented a case of parotid adenocarcinoma expressing the c-erbB-2 protein. In this case the adenocarcinoma was thought to have originated from pleomorphic adenoma. Immunohistochemically, the adenocarcinoma cells were stained and the remaining pleomorphic adenoma cells were not stained by polyclonal antibody against the c-erbB-2 protein. The expression of c-erbB-2 protein may have been related to the malignant development of the pleomorphic adenoma.
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PMID:Expression of c-erbB-2 protein detected in adenocarcinoma arising from parotid pleomorphic adenoma. 197 76

A system of histologic grade of malignancy in human breast carcinoma was devised by significantly modifying the way of evaluating number of mitoses and architectural atypia in the histologic grading of Bloom and Richardson. The modified grading system was applicable to all histologic subtypes of adenocarcinoma and showed a good association with prognosis of breast carcinoma patients in retrospective analysis of 176 consecutive surgical cases (P less than 0.0001). Of the three components of histologic grade, architectural atypia and number of mitotic figures independently had a significant effect on the prognosis. The copy number of c-erbB-2, a prognostic factor independent of tumor size and nodal status, was strongly correlated with the histologic grade, number of mitotic figures, and degree of nuclear atypia (P less than 0.001, each). Cox's regression model analysis showed that nodal status and histologic grade were two determinants of prognosis, and the independent effect of c-erbB-2 amplification was absorbed within that of the histologic grade. Although the importance of c-erbB-2 gene copy number seemed to be inferior to that of the histologic grade, both were shown to be strongly associated with the aggressiveness of the tumor itself rather than the extent of tumor spread.
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PMID:Correlation between histologic grade of malignancy and copy number of c-erbB-2 gene in breast carcinoma. A retrospective analysis of 176 cases. 215 4

We investigated the effect of an activated c-erbB-2 gene (also known as ERBB2) on metastatic potential. The c-erbB-2 gene was activated by mutation of the valine at position 659 within the transmembrane domain to glutamic acid. The activated c-erbB-2 expression vector was transfected into low-metastatic-potential NL-4 cells, which were established from a metastatic variant of murine colon adenocarcinoma 26. All 10 clones produced lung metastases in BALB/c mice injected via the tail vein. Eight of the 10 clones expressed messenger RNA (mRNA) of activated c-erbB-2 and showed morphological alteration; seven of the eight produced significantly enhanced experimental metastatic activity compared with that of untransfected NL-4 or NL-4neo cells, and one had metastatic ability similar to that of NL-4 cells. Two clones did not express c-erbB-2 mRNA and did not show morphological alteration or highly metastatic phenotype. Five of the 10 clones subcutaneously implanted in the flank failed to produce metastasis in the lungs or other organs of the mice. The metastatic ability of the other five clones was not determined. These results indicate that the activated c-erbB-2 gene can enhance experimental but not spontaneous metastatic potential in NL-4 cells, suggesting participation of the gene in the metastatic process after initial arrest and lodgement in the capillary bed.
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PMID:Low metastatic potential of clone from murine colon adenocarcinoma 26 increased by transfection of activated c-erbB-2 gene. 221 5

Estrogen-stimulated growth of the human mammary adenocarcinoma cell line MCF-7 is significantly inhibited by monoclonal antibodies to the epidermal growth factor (EGF) receptor that act as antagonists of EGF's mitogenic events by competing for high-affinity EGF receptor binding sites. These antibodies likewise inhibit the EGF or transforming growth factor-alpha (TGF-alpha)-stimulated growth of these MCF-7 cells. An analogous pattern of specific EGF or TGF-alpha growth inhibitory activity was obtained using a synthetic peptide analog encompassing the third disulfide loop region of TGF-alpha, but containing additional modifications designed for increased membrane affinity [( Ac-D-hArg(Et)2(31),Gly32,33]HuTGF-alpha(31-43)NH2). The growth factor antagonism by this synthetic peptide was specific in that it inhibited EGF, TGF-alpha, or estrogen-stimulated growth of MCF-7 cells but did not inhibit insulin-like growth factor-1 (IGF-1)-stimulated cell growth. Altogether, these results suggest that a significant portion of the estrogen-stimulated growth of these MCF-7 cells is mediated in an autocrine/paracrine manner by release of EGF or TGF-alpha-like growth factors. The TGF-alpha peptide likewise inhibited EGF- but not fibroblast growth factor (FGF)- or platelet-derived growth factor (PDGF)-stimulated growth of NIH-3T3 cells in completely defined media; but had no effect on growth or DNA synthesis of G0-arrested cells, nor did it effect growth of NR-6 cells, which are nonresponsive to EGF. Although this synthetic peptide did not directly compete with EGF for cell surface receptor binding, it exhibited binding to a cell surface component (followed by internalization), which likewise was not competed by EGF. The peptide did not directly inhibit EGF-stimulated phosphorylation of the EGF receptor, nor did it inhibit phosphorylation of an exogenous substrate, angiotensin II, by activated EGF receptor. The TGF-alpha peptide did, however, affect the structure of laminin as manifested by laminin self-aggregation; this affect on laminin may, in turn, have a modulatory effect on EGF-mediated cell growth.
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PMID:Inhibition of epidermal growth factor/transforming growth factor-alpha-stimulated cell growth by a synthetic peptide. 253 Feb 43


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