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)

Amplification and overexpression of erbB-2/neu is an important determinant in the initiation and progression of human breast cancer. Indeed, transgenic mice that over-express the neu proto-oncogene heritably develop mammary adenocarcinomas. Tumorigenesis in these transgenic strains is associated with activation of the intrinsic catalytic activity of Neu. In many of these tumors, activation of Neu occurs as a result of somatic mutations located within the transgene itself. Examination of the altered neu transcripts revealed the presence of in-frame deletions that encode aberrant Neu receptors lacking 5 to 12 amino acids within the extracellular domain proximal to the transmembrane region of Neu. In addition to these deletion mutants we have also detected single point mutations within this juxta-transmembrane region. The majority of the mutations analyzed affect the one of several conserved cysteine residues present within this region. Introduction of these activating mutations into the wild-type neu cDNA results in its oncogenic conversion. Taken together, these observations suggest that this cysteine-rich region plays an important role in regulating the catalytic activity of Neu.
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PMID:Oncogenic activating mutations in the neu/erbB-2 oncogene are involved in the induction of mammary tumors. 1066 81

The neu (c-erbB-2, Her-2) protooncogene is amplified and overexpressed in 20-30% of human breast cancers. Although transgenic mouse models have illustrated the role of Neu in the induction of mammary tumors, Neu expression in these models is driven by a strong viral promoter of questionable relevance to the human disease. To ascertain whether expression of activated Neu under the control of the endogenous promoter in the mammary gland could induce mammary tumors we have generated mice that conditionally express activated Neu under the transcriptional control of the intact endogenous Neu promoter. Expression of oncogenic neu in the mammary gland resulted in accelerated lobulo-alveolar development and formation of focal mammary tumors after a long latency period. However, expression of activated Neu under the normal transcriptional control of the endogenous promoter was not sufficient for the initiation of mammary carcinogenesis. Strikingly, all mammary tumors bear amplified copies (2-22 copies) of the activated neu allele relative to the wild-type allele and express highly elevated levels of neu transcript and protein. Thus, like human erbB-2-positive breast tumors, mammary tumorigenesis in this mouse model requires the amplification and commensurate elevated expression of the neu gene.
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PMID:Amplification of the neu/erbB-2 oncogene in a mouse model of mammary tumorigenesis. 1071 6

Clinical and epidemiological data have linked cervical cancer to the Human Papilloma Virus (HPV) infection. However, the presence of HPV infection alone is not enough to cause tumorigenesis, suggesting a role for additional host-cell genetic factors. The aim of the present work was to study the association of K-ras and c-erbB-2 mutations in cervical tissue samples with different grades of dysplasia and infected with HPV-6 ("low-risk" type) or HPV-16 and HPV-18 ("high-risk" types). Negative HPV-DNA samples were used as controls. The detection of K-ras and c-erbB-2 activation were performed by Artificial Refractory Mutation System (ARMS)-PCR and semiquantitative PCR, respectively. Statistical analysis showed a highly significant difference in K-ras codon 12 mutation frequency between high-risk and low-risk HPV-infected samples (p<0.05). On the other hand, amplification of the c-erbB-2 oncogene appeared associated to tissue samples infected with HPV-6 (p<0.003). Cervical carcinoma appears to arise from a series of well-characterized progressive histological changes, but the genetic alterations necessary for cervical tumorigenesis are not yet clear. These results raise the possibility for a role of certain proto-oncogenes and their activation in cervical neoplasia.
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PMID:Association between activated K-ras and c-erbB-2 oncogenes with "high-risk" and "low-risk" human papilloma virus types in preinvasive cervical lesions. 1094 49

Inactivation of the gene "deleted in colon cancer" (DCC) on chromosome 18 is known to be associated with the tumorigenesis and metastasis of colorectal cancer. In the present study, we investigated the expression of DCC, P53 and HER-2/neu product in surgical specimens from 79 patients with invasive breast cancer by immunohistochemistry staining and found the expression of DCC to be decreased in 42 tumors (52%). Overexpression of HER-2/neu and P53 was detected in 29 (36.8%) and 26 (32.9%) of this 79 breast cancer specimens, respectively. To evaluate the outcomes of the 79 breast cancer patients, we followed up the patients during the period from May 1990 to August 1998. The average length of follow-up was 52 months (ranging from 4 to 94 months). Patients with tumors having a combination of DCC-negative and HER-2/neu overexpression showed a marginal influence on survival time of breast cancer (P = 0.06). However, patients with tumors having a combination of DCC-negative and P53 overexpression showed no influence of these on survival time of breast cancer (P = 0.36). These findings suggest that a decreased DCC expression and HER-2/neu overexpression may influence the prognosis of breast cancer.
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PMID:The DCC protein expression in breast carcinoma. 1096 18

Recent evidence indicates that inherited and acquired genetic mutations are the driving force behind carcinogenesis and cellular transformation. This review examines a number of proto-oncogenes and tumor suppressor genes that are associated with ovarian carcinomas, including p53, BRCA1, and BRCA2; mismatch repair genes such as hMSH2 and hMLH1; and PTEN, HER-2/neu, K-ras, fms, and AKT2. Novel genes recently implicated in ovarian tumorigenesis are discussed, including NOEY2, OVCA1, and PIK3CA. Although no singular gene alteration has been shown to initiate transformation in the ovarian epithelium, elucidation of the complex molecular and cellular mechanisms involving these known gene mutations may result in new clinical management strategies.
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PMID:Genetic factors in ovarian carcinoma. 1112 66

Both the non-receptor tyrosine kinase, c-Src, and members of the epidermal growth factor (EGF) receptor family are overexpressed in high percentages of human breast cancers. Because these molecules are plasma membrane-associated and involved in mitogenesis, it has been speculated that they function in concert with one another to promote breast cancer development and progression. Evidence to date supports a model wherein c-Src potentiates the survival, proliferation and tumorigenesis of EGF receptor family members, in part by associating with them. Phosphorylation of the EGF receptor by c-SRC is also critical for mitogenic signaling initiated by the EGF receptor itself, as well as by several G-protein coupled receptors (GPCRs), a cytokine receptor, and the estrogen receptor. Thus, c-Src appears to have pleiotropic effects on cancer cells by modulating the action of multiple growth-promoting receptors.
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PMID:Tyrosine kinase signalling in breast cancer: epidermal growth factor receptor and c-Src interactions in breast cancer. 1125 Jul 11

Epithelial ovarian cancer is a heterogeneous disease and many biologic and molecular factors are important for its development and progression, including growth rate, metastatic potential, chemo- and radiosensitivity, and prognosis. Even in the early stages (FIGO I-II), many questions persist about the biologic behavior, optimal treatment, and prognosis. In a series of 106 patients with epithelial ovarian cancers in FIGO stages IA-IIC, a number of known prognostic factors (age, FIGO stage, histopathologic type, and tumor grade) were studied in relation to two important growth factor receptors for oncogenesis (HER-2/neu and EGFR). Immunohistochemical techniques were used. All patients received adjuvant radiotherapy 4-6 weeks after the primary surgery. In a univariate analysis, the expression of the HER-2/neu receptor was not associated with any of the clinicopathologic factors studied or survival status. Positive EGFR staining was associated with poor survival in a univariate analysis. Co-expression of HER-2/neu and EGFR was most frequently seen in serous tumors and positive staining for HER-2/neu alone was associated with mucinous tumors. Both endometrioid and clear cell tumors belonged to the largest subgroup with concomitant negativity for both HER-2/neu and EGFR. In a multivariate Cox analysis, the tumor grade and EGFR status of the tumors were independent and significant prognostic factors. A therapeutic strategy for epithelial ovarian cancer might be to decrease EGFR expression by gene therapy in combination with adjuvant radiotherapy or chemotherapy.
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PMID:The growth factor receptors HER-2/neu and EGFR, their relationship, and their effects on the prognosis in early stage (FIGO I-II) epithelial ovarian carcinoma. 1132 10

Chromosome 17q is highly susceptible to rearrangement mutations in breast cancer. c-erbB-2 at 17q11.2 approximately q21.1 is frequently amplified, as is a region at 17q22 approximately q24. As a step in the search for the target gene(s) of the 17q22-q24 amplification we determined whether the placental lactogen (PL) genes at 17q23 were amplified in 59 breast carcinomas. These genes were selected as their upregulation could theoretically be involved in breast cancer tumorigenesis. Amplification of the PL genes, and also of c-erbB-2, was detected using semi-quantitative PCR. The reliability of this method was confirmed since c-erbB-2 results obtained using PCR, Southern blotting and immunohistochemistry were in good agreement. The PL genes were amplified in 13 (22%) of the tumors. Furthermore, the PL and c-erbB-2 genes were frequently co-amplified although there is a non-amplified region between them. Expression of PL was investigated in 26 tumors and was detected in 16 of these cases including all 10 tumors with amplification of the PL genes. The tumors with PL gene amplification were all aneuploid. A trend was seen towards an increased incidence of lymph node involvement for tumors with amplification of the PL genes and for tumors with co-amplification of PL and c-erbB-2, which suggests a possible association with high malignancy.
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PMID:Frequent co-amplification of two different regions on 17q in aneuploid breast carcinomas. 1140 59

Twenty-six patients, meeting strict criteria for primary peritoneal serous papillary carcinoma (PPSPC), were matched to 22 patients with ovarian serous papillary cancer (OSPC) for age and stage. Immunohistochemistry was used to determine the status of estrogen receptors (ER), progesterone receptors (PR), the expression of cell proliferation marker Ki-67, and the overexpression of HER-2/neu and p53 protein. Of the PPSPCs, 53.8% were poorly differentiated, as were 18.2% of the OSPCs (p = 0.012). Positive immunostaining for ER and PR was less in PPSPCs (30.8% and 46.2%, respectively) than OSPCs (72.7% and 90.9%; p = 0.003 and p = 0.001, respectively). Conversely, a significant increase in the expression of Ki-67 was found in PPSPCs (37.7%) versus OSPCs (26.8%) (p = 0.039). The same trend was found for HER-2/neu, being overexpressed in 38.5% of the PPSPC versus 9.1% of the OSPCs (p = 0.019). Overexpression of p53 was found in 30.8% of the PPSPCs and 45.4% of the OSPCs (not significant). There was a significantly worse survival rate for PPSPCs than for OSPCs (p = 0.017), yet none of the studied parameters were significantly correlated with survival within the PPSPC and OSPC groups. The significantly different immunohistochemical expression of ER, PR, Ki-67, and HER-2 in PPSPCs compared with OSPCs suggests that different molecular events may lead to tumorigenesis in these two cancers.
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PMID:Immunohistochemical comparison of primary peritoneal and primary ovarian serous papillary carcinoma. 1160 17

Activation of the epidermal growth factor receptor (EGFR) family is thought to play a critical role in both embryogenesis and oncogenesis. The diverse biological activities of the EGFR family are achieved through various ligand-receptor and receptor-receptor interactions. One receptor that has been found to play a central role in this signaling network is ErbB-2/Neu, and it is considered the preferred heterodimerization partner for other members of the EGFR family. To assess the importance of the catalytic activity of ErbB-2 in embryonic development, we have generated mice expressing a kinase-dead erbB-2 cDNA under the transcriptional control of the endogenous promoter. Here, we show that mice homozygous for the kinase-dead erbB-2 allele die at midgestation and display the same spectrum of embryonic defects seen in erbB-2 knockout mutants. These observations suggest that the catalytic activity of ErbB-2 is essential for normal embryonic development.
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PMID:The catalytic activity of the ErbB-2 receptor tyrosine kinase is essential for embryonic development. 1180 99


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