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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The etiology of cancer is a complex interplay of various factors, including genetic alterations. Multiple studies have been carried out to identify and characterize mutations that frequently occur during tumorigenesis. In human breast cancer, amplification of proto-oncogenes (c-myc, c-erbB-2/neu) and chromosome 11q13, mutation of p53 and loss of heterozygosity (chromosomes 1, 3p, 6q, 7q, 11p, 13q, 16q, 17, 18q and 22q) represent the major types of genetic abnormalities that have been frequently observed in tumor DNAs. The genetic deletions and mutations could inactivate tumor-suppressor genes. In some studies, specific alterations have been associated with some clinical parameters. Recently, linkage analyses, on large families with a predisposition to breast cancer, have been performed to map putative breast cancer susceptibility genes. The survey of high risk patients should be organised to make an earlier diagnosis.
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PMID:[Molecular analysis of breast cancers: recent developments]. 130 32

The c-erbB-2 (HER-2/neu) protein is a membrane glycoprotein growth factor receptor showing molecular homology with the epidermal growth factor receptor (EGFR). We examined the immunohistochemical reactivity of monoclonal antibodies against both of these proteins in normal surface epithelium, surface inclusion cysts, and common epithelial tumours of the ovary. The ovarian tumours were classified as benign (16), borderline malignant (2), and malignant (19). Normal surface ovarian epithelium was weakly positive for both c-erbB-2 protein and EGFR. In surface inclusion cysts, however, the epithelial cells lining the lumen exhibited stronger staining for c-erbB-2 protein, but no staining for EGFR. All 16 benign ovarian tumours and the 2 borderline malignant ovarian tumours were positive for c-erbB-2 protein and negative for EGFR. Of the ovarian carcinomas, 13 of the 19 (68.4%) were positive for c-erbB-2 protein and negative for EGFR, while 4 showed positivity for both c-erbB-2 protein and EGFR. Two cases were negative for both proteins. Expression of both c-erbB-2 protein and EGFR was found in endometrioid carcinoma with squamous differentiation and in clinically advanced poorly differentiated serous carcinomas. Expression of c-erbB-2 protein appears to be increased and that of EGFR is reduced in the early stage of epithelial ovarian oncogenesis. The expression of EGFR with c-erbB-2 protein in ovarian carcinoma is related both to histological differentiation and/or advanced clinical stage.
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PMID:Immunohistochemical localization of c-erbB-2 protein and epidermal growth factor receptor in normal surface epithelium, surface inclusion cysts, and common epithelial tumours of the ovary. 136 Jul 20

Tumorigenesis is a multistep process involving mutations of dominantly acting proto-oncogenes and mutations and loss-of-function mutations of tumor suppressor genes. Some of these mutations may be inherited, but most of them are acquired. Models for the sequential steps of the genetic changes involved in tumor development have been proposed for certain cancers, such as colon cancer. In the case of ovarian cancer, relatively little is known about the genetic events associated with the initiation or subsequent progression and metastases of the tumor. Cytogenetic analysis has revealed a high incidence of both structural and numerical chromosome changes, and the extent of these changes seems to increase with tumor progression. Oncogene activations of the proto-oncogenes K-ras, c-myc and c-erbB-2 have been found more frequently in aggressive ovarian tumors and may be associated with poor survival. Tumor-specific allele loss involving putative tumor suppressor genes has been observed for loci at chromosomes 11p, 17p, and 17q,--loci commonly deleted in other cancers too. A relatively high incidence of allelic loss on chromosome 6q appears to be specific to ovarian carcinoma. Familial breast/ovarian cancer has been suggested to map to chromosome 8q. Recently we have found a germ-line mutation in the tumor suppressor gene p53 in a family with breast- and ovarian cancers, indicating that this is the predisposing gene in this family. Genetic changes important for the etiology of ovarian cancers seem to involve both somatic mutations of oncogenes and somatic or germ-line inactivation of tumor suppressor genes.
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PMID:Oncogenesis in ovarian cancer. 150 89

Using the 21N polyclonal antibody, we immunohistochemically stained 314 primary breast carcinomas to identify those tumors overexpressing the c-erbB-2 oncoprotein and to ascertain the prognostic significance of this expression on disease-free and overall survival. Positive membrane staining was present in 52 (17%) of these carcinomas of which 7 (13%) were ductal carcinomas in situ. There was no significant relationship between c-erbB-2 positivity and (a) age at diagnosis, (b) menopausal status, (c) tumor size, (d) lymph node status, (e) estrogen receptor status, or (f) whether or not the patient had disseminated disease outside the axillary fields. However, c-erbB-2-positive tumors were significantly associated with poorer grade (P = 0.02). Patients who were positive for this oncoprotein had a shorter disease-free survival (P = 0.002) and reduced overall survival (P = 0.0001). Overexpression of this oncoprotein was predictive of a worse prognosis in lymph node-positive disease (P = 0.003) and in patients presenting with grade II tumors (P = 0.001). Stratifying the patients on the basis of estrogen receptor status suggested that c-erbB-2+/estrogen receptor-negative status was predictive of a poorer prognosis when compared with the other subgroups (P less than 0.001). Primary and recurrent tumor tissues were available from 42 of the 314 patients. Identical patterns of c-erbB-2 expression occurred in 95% of cases, arguing against a direct role for c-erbB-2 expression in the process of tumor dissemination. The high incidence of staining in ductal carcinomas in situ suggests that expression of this oncoprotein is an early event in tumorigenesis. Finally, multivariate analysis indicated that the c-erbB-2 oncoprotein was an independent prognostic indicator for overall survival in breast carcinoma patients.
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PMID:Prognostic significance of c-erbB-2 and estrogen receptor status in human breast cancer. 167 98

The development of malignant tumors of the peripheral nervous system (schwannomas) within a defined intracranial section of the rat trigeminal nerve ("trigeminal box") was used as a model to identify genetic alterations typically associated with the process of cell-lineage-specific oncogenesis induced by exposure to N-ethyl-N-nitrosourea on postnatal day 1. All 47 trigeminal schwannomas (and 12 extracranial neurinomas) investigated carried a T.A----A.T transversion mutation at nucleotide 2012 of the neu (erbB-2) gene sequence encoding the transmembrane domain of pg185neu. This mutation was absent in all 18 tumors in the brain and spinal cord (central nervous system) isolated from the same animals. Identical observations were made in cell lines derived from N-ethyl-N-nitrosourea-induced rat schwannomas vs. brain tumors. By asymmetric PCR and mutant-specific Mnl I restriction fragment length analyses, cells carrying the mutant neu allele became detectable and could be localized within the trigeminal box as early as 7 days after the carcinogen pulse. The proliferation rate of the mutant cells strongly exceeded that of the wild-type cells up to the time of maturation of the trigeminal nerve around postnatal day 30 and thereafter to a lesser extent until the appearance of schwannomas. A specific mutation of the neu gene thus represents a very early, probably the first, step in the malignant conversion of immature rat Schwann cells exposed to N-ethyl-N-nitrosourea in vivo and is diagnostic for a subset of proliferative cells at high risk of progressing toward the expression of fully malignant phenotypes. Loss of heterozygosity for the mutant neu allele is a candidate event for a critical second step in the process.
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PMID:Early mutation of the neu (erbB-2) gene during ethylnitrosourea-induced oncogenesis in the rat Schwann cell lineage. 168 25

A novel multiparameter flow-cytometric method was used to quantify the expression of epidermal growth factor receptor (EGFR) and c-erbB-2 oncoprotein on 85 cryopreserved normal tissues (30 ovary, 29 endometrium, 16 cervix) and 67 carcinomas (31 ovarian, 18 cervical, 15 endometrial, 3 vulvar). Overexpression of the EGFR and c-erbB-2 oncoproteins was found in respectively 3/31 (9%) and 10/31 (32%) ovarian carcinomas, 13/18 (72%) and 7/18 (38%) cervical carcinomas, and 2/15 (13%) and 2/15 (13%) endometrial carcinomas. Oncoprotein expression was significantly higher in the malignant tumors (for all tumor sites) than in the corresponding normal tissues (P less than 0.034 for all combinations). Aneuploid tumors expressed levels of EGFR and c-erbB-2 oncoprotein significantly higher than those of DNA diploid tumors (P = 0.042 and P = 0.048, respectively). Oncoprotein could be detected in nearly all normal tissues: expression was higher in premenopausal than in postmenopausal patients (EGFR, P = 0.07; c-erbB-2, P less than 0.001). The present study supports the idea that EGFR and c-erbB-2 may play an important role in the autocrine, paracrine, and/or endocrine growth control and differentiation of normal tissues. Alteration in the expression of these oncoproteins is probably involved in malignant transformation and tumorigenesis.
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PMID:Multiparameter flow-cytometric quantitation of epidermal growth factor receptor and c-erbB-2 oncoprotein in normal and neoplastic tissues of the female genital tract. 168 31

To evaluate epidermal growth factor (EGF) receptor expression in the neoplastic process of squamous cell epithelium of the uterine cervix, normal, premalignant, and malignant cervical tissues were examined for the presence of EGF receptor by the avidin-biotin immunoperoxidase techniques with a monoclonal antibody to EGF receptor. Although normal cervical epithelium did not show appreciable staining for EGF receptor, predominant staining for the receptor was observed in most dysplastic epithelia and carcinomas in situ. In invasive squamous carcinoma, there was a great difference in the immunohistochemically detected levels of EGF receptor among the histologic cell types. Large cell nonkeratinizing carcinoma and its keratinizing counterpart contained high levels of EGF receptor; small cell nonkeratinizing carcinoma lacked immunostainable EGF receptor. These results suggest that the elevated expression of EGF receptor may be involved in the initial stage of tumorigenesis of cervical squamous epithelium and that EGF receptor expression may be related to the differentiation or dedifferentiation of cervical squamous carcinoma cells.
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PMID:Immunohistochemical demonstration of elevated expression of epidermal growth factor receptor in the neoplastic changes of cervical squamous epithelium. 173 18

Overexpression of the p185 product of the c-erb B2/neu gene is correlated with cell transformation and tumorigenesis. To study expression of this gene, a 1548-base pair fragment (-1571 to -24 bp relative to the ATG initiator codon) of the human c-erb B2/neu 5'-noncoding region was isolated, sequenced, and analyzed with respect to basal and inducible activity using the luciferase expression vector pSVOAL delta 5'. This fragment contained an Alu repetitive element which was confirmed in two independent clones. Basal activity of the 1548-base pair fragment was equivalent to the epidermal growth factor receptor promoter region and 32 and 16% as active as the Herpes simplex thymidine kinase and Rous sarcoma virus promoters, respectively. Induction of luciferase activity was observed in response to epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate, dibutyryl cAMP, and retinoic acid. Additive and synergistic responses with more than 30-fold increases were observed after treatment with combinations of inducing agents, indicating complex regulation of this gene. These results show that the promoter region of the c-erb B2/neu gene contains sequences that dictate regulatory responses to several environmental signals.
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PMID:Structure and inducible regulation of the human c-erb B2/neu promoter. 196 58

Evidence that the c-erbB-2 proto-oncogene is important in prognosis and oncogenesis in a number of human malignancies is increasing. DNA (Southern) hybridization and immunoblotting (Western) techniques are most commonly utilized to determine the amplification and protein expression of this proto-oncogene, respectively. These extraction techniques are often time consuming, costly, and subject to variability depending on the histological characteristics of the tumor. Immunohistochemistry (IHC), on the other hand, is more often time and cost effective. In addition, IHC may offer enhanced sensitivity over extraction techniques because of the in situ nature of analysis. In data presented here, 71 cases of human mammary carcinoma were concomitantly assessed for c-erbB-2 gene copy number and oncoprotein expression by dilution DNA hybridization and IHC, respectively. In 65 (92%) of 71 cases, high-level expression was associated with gene amplification, whereas moderate or low-level expression was associated with a normal diploid gene copy number. In five of the six discrepant cases, IHC predicted amplification which was not corroborated by Southern analysis. In these cases, tumor mass was limited by the intraductal component of the lesion or by an abundance of stromal elements within the specimen. In 39 of the 71 total cases, Western immunoblotting was compared with IHC in the assessment of oncoprotein expression. Concordance was found in 33 (85%) of 39 cases. In four of the six discrepant cases, high levels of c-erbB-2 expression were demonstrated by IHC but not by immunoblotting. In these cases, intraductal disease and stroma-rich tumors again led to a relative paucity of neoplastic tissue within the specimens. We conclude that IHC offers a favorable alternative to either Southern analysis or Western immunoblotting in the assessment of c-erbB-2 gene copy number and expression levels of oncoprotein in human mammary carcinoma. Furthermore, IHC may prove advantageous to either extraction technique in specimens with limited tumor mass, such as biopsy materials, stroma-rich tumors, or early stage lesions such as intraductal carcinoma.
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PMID:c-erbB-2 expression in breast cancer detected by immunoblotting and immunohistochemistry. 197 42

The expression of the erbB-2 gene product was studied immunohistochemically on 38 normal colonic mucosae, 14 adenomas and 44 colon cancers, with the use of two anti-erbB-2 antibodies, a rabbit polyclonal antibody specific for the intracellular domain and a mouse monoclonal antibody specific for the extracellular domain. Normal mucosae and adenomas were not stained. Five cases (11%) of colon cancer were positive with the polyclonal anti-erbB-2 antibody, while only one case was positive with the monoclonal antibody. Most of the positive cases were in Dukes C stage. The rare overexpression of the erbB-2 protein in colon cancer seems to indicate a minor role for the gene in colorectal tumorigenesis.
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PMID:erbB-2 gene expression in colorectal cancer. 198 87


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