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 c-erbB-2/neu gene encodes a transmembrane protein of 185 kDa (p185) with tyrosine kinase activity and extensive sequence homology to epidermal growth factor receptor. Amplification and overexpression of the c-erbB-2/neu gene has been shown in certain human tumors and is postulated to be important in human carcinogenesis. High levels of expression of the c-erbB-2/neu gene have been reported in non-small-cell lung cancer (NSCLC) cell lines and primary tumors from the United States. Since geographical and cultural factors may contribute to the development of certain types of cancer, we examined p185 examined p185 expression in 120 tumors from Chinese patients with lung cancers of different cell types and used immunohistochemical staining to determine the extent and general significance of p185 expression in human primary lung cancer. Our results demonstrate that 58.8% of the NSCLCs expressed p185 and that expression of p185 was observed only in NSCLC and not in small-cell lung cancers. Thirty-three of 41 adenocarcinomas and 24 of 55 squamous cell carcinomas among the NSCLCs examined were found to express p185 at levels different from those of normal lung. For the squamous cell carcinomas, p185 expression was correlated with lymph node metastasis (P less than 0.01), but for the adenocarcinomas, it was not (P greater than 0.05). In addition, expression of p185 in NSCLC was significantly more frequent in patients in advanced clinical stages. Our findings indicate that p185 expression is a frequent event and a general phenomenon in NSCLC and is correlated with poor clinical prognostic indicators, suggesting that expression of p185 may be of potential prognostic importance in NSCLC.
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PMID:Overexpression of the c-erbB-2/neu-encoded p185 protein in primary lung cancer. 135 Jan 98

The proto-oncogene designated erbB2 or HER2 encodes a 185-kilodalton transmembrane tyrosine kinase (p185erbB2), whose overexpression has been correlated with a poor prognosis in several human malignancies. A 45-kilodalton protein heregulin-alpha (HRG-alpha) that specifically induced phosphorylation of p185erbB2 was purified from the conditioned medium of a human breast tumor cell line. Several complementary DNA clones encoding related HRGs were identified, all of which are similar to proteins in the epidermal growth factor family. Scatchard analysis of the binding of recombinant HRG to a breast tumor cell line expressing p185erbB2 showed a single high affinity binding site [dissociation constant (Kd) = 105 +/- 15 picomolar]. Heregulin transcripts were identified in several normal tissues and cancer cell lines. The HRGs may represent the natural ligands for p185erbB2.
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PMID:Identification of heregulin, a specific activator of p185erbB2. 135 Mar 81

Expression of the c-erbB-2 proto-oncogene is inhibited by oestrogens in oestrogen-responsive human breast cancer cells, at both mRNA and protein level. Here we report that, where the regulation of c-erbB-2 is concerned, tamoxifen displays a full anti-oestrogenic activity, enhancing the expression of c-erbB-2 in oestrogen receptor-positive cells cultured with untreated fetal calf serum or reversing the inhibitory effect of added oestrogens. Meanwhile, tamoxifen strongly inhibited cell growth. Tamoxifen was inactive on both c-erbB-2 expression and growth of oestrogen receptor-negative cells. These results may have important implications to explain occasional failure of tamoxifen therapy in oestrogen receptor-positive breast cancers.
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PMID:Tamoxifen up-regulates c-erbB-2 expression in oestrogen-responsive breast cancer cells in vitro. 135 Apr 52

Amplification of the proto-oncogene HER-2/neu and/or overexpression of the transmembrane protein p185erbB2 that it encodes occur in approximately 30% of human breast and gynaecological cancers seen clinically and are strongly associated with an unfavourable outcome. We report on the use of a new monoclonal antibody (Mab-145ww) together with immunoblotting for detection of p185erbB2 in membranes that remain after routine processing of breast cancer tissue for steroid receptor assays. Human breast cancer cell lines SKBR3 and MCF-7 were used as high and low controls, respectively, for p185erbB2 expression. Mab-145ww was detected p185erbB2 in more than half of the breast cancer specimens; the expression was intense in SKBR3 cells, but only faint in MCF-7 cells. These results demonstrate that routine processing of cancer tissue for steroid receptor status can include providing a preparation with which to assess p185erbB2 expression and, thus, can provide information potentially useful for the clinical management of individual cancer patients.
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PMID:Detection of the HER-2/neu proto-oncogene protein p185erbB2 by a novel monoclonal antibody (MAB-145ww) in breast cancer membranes from oestrogen and progesterone receptor assays. 135 Apr 53

Overexpression of c-erbB-2 occurs in 60% of in situ and 25% of infiltrating ductal carcinomas. We have previously found very strong associations between immunohistochemical staining for c-erbB-2 and histological pattern and nuclear size in ductal carcinoma in situ (DCIS) and less strong correlation with proliferative activity. In a further study of infiltrating ductal carcinomas we have found that, in addition to tumours arising from c-erbB-2 positive, large celled, rapidly proliferating, comedo carcinomas and c-erbB-2 negative small celled cribriform/micropapillary carcinomas with a low proliferative rate, there is a third group of c-erbB-2 negative tumours with large nuclei and variable proliferative activity. These latter tumours are not seen in pure DCIS suggesting that they have a very transient in situ stage. Therefore, although in pure DCIS c-erbB-2 positively appears to be associated with tumours with a greater invasive potential, and c-erbB-2 negativity with tumours having a more favourable prognosis, the latter is not necessarily true in infiltrating disease.
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PMID:Overexpression of the c-erbB-2 oncoprotein: why does this occur more frequently in ductal carcinoma in situ than in invasive mammary carcinoma and is this of prognostic significance? 135 Apr 56

The relationship was assessed between c-erbB-2 oncoprotein expression and other prognostic factors in breast cancer, such as axillary and internal mammary node metastases. The value of these indicators was analyzed in estimating prognosis, especially in patients with axillary node-positive breast cancer. These results showed that c-erbB-2 is significantly related to clinical stage and axillary node metastases. A univariate study revealed that disease-free and overall survival were correlated significantly with clinical stage, tumor size, axillary and internal mammary node metastases, and 21N status. Among the patients with axillary node involvement, however, 21N status did not appear to be a significant additional prognostic factor. Internal mammary node metastases were significant. In a multivariate study, only axillary and internal mammary node metastases were significant prognostic factors for either the entire group of patients or those with positive axillary nodes. Therefore, axillary node dissection and biopsy of the internal mammary nodes may provide important prognostic information for patients with breast cancer.
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PMID:C-erbB-2 oncoprotein expression versus internal mammary lymph node metastases as additional prognostic factors in patients with axillary lymph node-positive breast cancer. 135 May 4

Cowden's disease (multiple hamartoma syndrome) is characterized by multiple hamartomas of ectodermal, endodermal, and mesodermal origin, a high incidence of malignant tumors of the breast and/or thyroid gland, and an autosomal dominant pattern of inheritance. Similar to sporadic breast cancer, chromosomal studies have not elucidated the cause of this syndrome. The authors report the case of a patient with this syndrome and analyze the pattern of amplification or rearrangement of three genes: the HER-2/neu oncogene, the ras oncogene, and the estrogen-inducible gene, pS-2. All three of these genes were present in single copies without translocations. It was noteworthy that three of the most important genes currently studied in relation to breast cancer existed in a unamplified unrearranged state in this patient. Those with clinical manifestations of Cowden's disease may be candidates for prophylactic bilateral total mastectomy, and the authors recommend that these patients undergo this procedure by their third decade of life. An alternative to this approach would entail monthly self examinations, breast examinations by the patient's physician every 3 months, bilateral mammograms every 6 to 12 months, and biopsy of any suspicious lesions. It is crucial, however, that these patients be identified by their mucocutaneous lesions and family history before an underlying malignant lesion develops.
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PMID:Cowden's disease. A case report with analyses at the molecular level. 135 May 5

The neu oncogene has been demonstrated to be a potent transforming gene in rodent fibroblasts. The overexpression of the human erbB-2/neu oncogene has been implicated in the development and/or prognosis of several human carcinomas including that of the prostate. To assess the transforming potential of the activated rat neu oncogene in prostatic epithelial carcinogenesis, this laboratory has transfected a cloned non-tumorigenic, rat ventral prostate epithelial cell line, NbE-1.4, with an activated, point-mutated neu oncogene. Transfection of NbE-1.4 cells with the activated neu oncogene expression vector, pSV-neu-T (neu-T), resulted in an altered cell morphology, an increase in soft agar colony-forming efficiency, and conversion to a tumorigenic phenotype. Although the parental NbE-1.4 cells expressed endogenous c-neu mRNA, a reverse transcriptase polymerase chain reaction assay determined that the neu-T-transfected clones expressed only the point-mutated neu-T mRNA. The suppression of the c-neu transcripts occurred regardless of the neu-T mRNA level expressed in these cell clones. These data provide evidence to show that low-level expression of an activated neu oncogene alone was insufficient to transform rat prostate epithelial cells. Rather, overexpression of an activated neu oncogene correlated well with the acquisition of a tumorigenic phenotype by the NbE-1.4 epithelial cell line.
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PMID:Acquisition of a tumorigenic phenotype by a rat ventral prostate epithelial cell line expressing a transfected activated neu oncogene. 135 May 10

Expression of c-erbB-2 protein in carcinoma tissue was examined in 56 patients suffered from gastric carcinoma, and the correlation between the expression of c-erbB-2 protein and clinico-pathological factors, DNA ploidy pattern was also examined. Positive expression of c-erbB-2 protein in carcinoma tissue was detected in 21/56 (37.5%) cases, and the positive rate (71.4%) in tissue of differentiated carcinoma (pap, tub1, tub2) was significantly higher than that in tissue of undifferentiated carcinoma (por, sig, muc) (28.6%). No good correlation between the expression of c-erbB-2 in tissue and other clinico-pathological factors, such as ly, v, n, tumor size, stage of the tumor, and the location of the tumor was observed. In DNA ploidy, 70.6% of cases was aneuploid pattern, and 29.4% of cases was diploid pattern in positive expression of c-erbB-2 protein in carcinoma tissue. These results suggest that expression of c-erbB-2 protein is involved in promoting DNA synthesis in initial step of differentiated gastric carcinoma. The concentration of c-erbB-2 in serum of positive expression of c-erbB-2 protein in tissue was significantly higher than that in serum of negative expression of c-erbB-2 protein in tissue. Good correlation between serum concentration of c-erbB-2 protein and clinical stage of the carcinoma was observed in positive expression of c-erbB-2 protein in carcinoma tissue. The concentration of c-erbB-2 protein in serum can be a sensitive indicator for guess the Stage of the gastric carcinoma that express c-erbB-2 protein in carcinoma tissue.
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PMID:[Expression of c-erbB-2 protein in gastric carcinomas--correlation between immunohistochemical study and clinico-pathological factors, DNA ploidy pattern and concentration of c-erbB-2 protein in serum]. 135 Jun 46

Computer-assisted image analysis was used to demonstrate in exponentially proliferating human tumor cells the uneven postmitotic apportionment of several oncogene-encoded proteins (ras p21; erbB-2 p185; fos p55; myc p62). This observation may provide the explanation for the high degree of heterogeneity of postmitotic cells and the asynchrony in cell cycle traverse of cultured cells.
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PMID:Asymmetric distribution of oncogene products at mitosis. 135 Jun 77


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