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

We explored the mechanism of antigrowth action of Curcumin by investigating its effect on epidermal growth factor (EGF) receptor intrinsic kinase activity in the human epidermoid carcinoma A431 cells. The short-term treatment of cells with Curcumin inhibited EGF receptor intrinsic kinase activity up to 90% in a dose- and time-dependent manner, and also inhibited EGF-induced tyrosine phosphorylation of EGF receptors. The observed early effects of Curcumin were mediated via a cellular mechanism(s), and preceded the period when inhibition of cell growth occurred.
Biochim Biophys Acta 1994 Dec 30
PMID:Inhibitory effect of curcumin on epidermal growth factor receptor kinase activity in A431 cells. 780 21

Overexpression of HER-2/neu, a 185-kDa tyrosine kinase growth factor receptor, in human ovarian cancers has been correlated with a poor prognosis for survival of the disease. Previous studies have demonstrated that dexamethasone (Dex) induces a dose-dependent increase in HER-2/neu mRNA levels in the ovarian cancer cell line SK-OV-3 by stabilizing the HER-2/neu message. We extended these studies to test whether estrogen (Es), progesterone (Pr), and Dex were capable of regulating HER-2/neu mRNA levels in the human ovarian cancer cell lines NIH:OVCAR-3, SW 626, OVCA 433, and Caov-3. Southern blotting demonstrated that all four cell lines contained a single copy of the 12.5-kb HER-2/neu gene. Blotting techniques demonstrated low to barely detectable levels of HER-2/neu mRNA and protein in these cell lines. To determine whether steroids regulated HER-2/neu expression, all four ovarian cancer cell lines were cultured in the presence of 1 x 10(-7) M Es, Pr, or Dex and Northern blotting was completed. Unlike SK-OV-3 cells, the cell lines tested did not respond to the steroid treatments with alterations in their HER-2/neu mRNA levels. In conclusion, neither Es, Pr, nor Dex regulates HER-2/neu mRNA levels in NIH:OVCAR-3, SW 626, OVCA 433, and Caov-3 ovarian cancer cells. Future therapeutic manipulations of HER-2/neu should not involve hormonal intervention.
Gynecol Oncol 1994 Dec
PMID:Steroid hormonal independence of HER-2/neu mRNA expression in four human ovarian carcinoma cell lines. 783 82

Atypical alveolar hyperplasia (AAH) has recently been described in human lungs in association with primary lung cancer, particularly adenocarcinoma. Unlike proximal bronchogenic carcinoma, peripheral (parenchymal) adenocarcinoma of the lung does not have a well-recognized progenitor lesion. Epidemiological morphometric, and cytofluorometric data in the literature suggest that AAH is a candidate premalignant entity. In this study, 97 AAH lesions were found in lungs resected from 29 patients (1-13 lesions per case, mean 3.5) being treated for presumed carcinoma (25/29 had adenocarcinoma). From a study case-load of 285 adenocarcinoma-bearing lungs, the AAH incidence was 8.8 per cent. Sections of 67 AAH lesions from 19 patients were stained using monoclonal antibodies against Ki67 (MIB1), p53 (DO7), and c-erbB-2 (NCL-CB11). Ki67 was expressed in up to 10 per cent of AAH nuclei. Thirty-nine lesions (58 per cent) showed stainable p53 protein, while five (7 per cent) expressed membrane c-erbB-2 oncoprotein. These latter five lesions were all strongly positive for p53, and both p53 and c-erbB staining was associated with increased cellular crowding and pleomorphism in AAH. These data demonstrate that AAH exhibits some genetic changes associated with malignancy and thereby support the hypothesis that AAH is premalignant.
J Pathol 1994 Dec
PMID:Atypical alveolar hyperplasia: relationship with pulmonary adenocarcinoma, p53, and c-erbB-2 expression. 788 86

The prognostic significance of the three genes most frequently amplified in breast tumors was investigated by multivariate analysis in a retrospective study of 112 primary human breast cancers. These three genes, c-myc, int-2/FGF3 (a marker for the 11q13 amplicon), and c-erbB-2/neu, were amplified in 37%, 14%, and 10% of breast tumors studied, respectively. Amplification of the c-myc gene was not related to metastasis-free survival in the total population but was a discriminant prognostic indicator in premenopausal patients. Int-2/FGF3 gene amplications were good indicators of prognosis, especially in premenopausal patients, and also in lymph-node-positive and steroid-receptor-negative patients. Int-2/FGF3 amplification and progesterone receptor status together proved to be the only independent variable predictive of metastasis-free survival. The risk of relapse in the subgroup of progesterone-receptor-negative patients was 5 times greater for those with int-2/FGF3 amplification than for those without this alteration. Amplifications at the c-erbB-2/neu locus were not significantly associated with any standard prognostic indicator or with an increased risk of recurrence. These results suggest that the combined use of classical prognostic factors and molecular markers may improve prognostic value and be applicable to patients with specific tumor phenotypes.
Mod Pathol 1994 Dec
PMID:Int-2/FGF3 amplification is a better independent predictor of relapse than c-myc and c-erbB-2/neu amplifications in primary human breast cancer. 789 57

The HER4/ERBB4 gene encodes a 180K transmembrane protein (HER4/p180erbB4) that is structurally related to the 185K product (HER2/p185erbB2) of the HER2/ERBB2 proto-oncogene. A 45K heparin-binding glycoprotein (p45) has been characterized that specifically activates the intrinsic tyrosine kinase activity of HER4 (ref. 2). This HER4 ligand shares several features with the heregulin family of proteins, including molecular mass, ability to induce differentiation of breast cancer cells, activation of tyrosine phosphorylation in MDA-MB453 cells, and amino-terminal protein sequence. Heregulin exists as multiple isoforms and all are presumed to interact directly with HER2 (refs 3-6). We have used binding and phosphorylation studies with recombinant ligand on cell lines expressing recombinant receptors, and report here that heregulin, like p45, is a specific ligand for HER4. Furthermore, heregulin fails to induce phosphorylation of HER2 in the absence of HER4. These findings suggest that activation of the HER4 receptor is involved in signal transduction by heregulin.
Nature 1993 Dec 02
PMID:Heregulin induces tyrosine phosphorylation of HER4/p180erbB4. 790 37

Correlation of c-erbB-2 protein (n = 44), epidermal growth factor receptor (EGFR) (n = 41) expression, and DNA ploidy pattern (n = 42) with clinical outcomes of human colorectal cancers was studied. Using monoclonal antibodies against c-erbB-2 protein and EGFR, an immunohistochemical study of the expression of c-erbB-2 protein and EGFR in frozen tissue sections from the lesion was performed. There was no significant correlation between the expression of c-erbB-2 protein and clinicopathological findings such as, tumor size, histological type, depth of invasion, lymph node metastasis, lymphatic vessel invasion, or venous invasion. However, the incidence of c-erbB-2 protein expression in Dukes D was significantly higher (9/10, 90%) than that in Dukes A to C (16/34, 47.1%). Similar tendency was also observed in the expression of EGFR. Aneuploid case was observed in 12 of observed 25 (48%) cases without lymph node metastasis, while it was observed in 16 of 17 cases (94.1%) with lymph node metastasis and there was significant association between DNA ploidy pattern and lymph node metastasis (P < 0.01) and most of the cases (17/20, 85%) were aneuploidy in Dukes C and D. The results above suggest that the expression of c-erbB-2 protein or EGFR was associated with distant metastasis, while on the other hand DNA ploidy pattern was correlated with lymph node metastasis.
J Surg Oncol 1993 Dec
PMID:Study of c-erbB-2 protein and epidermal growth factor receptor expression and DNA ploidy pattern in colorectal carcinoma. 790 86

Four monoclonal antibodies (MAbs) specific for the extracellular domain of the human erbB-2/HER2 protein (FRP5, FSP16, FWP51 and FSP77) have been isolated (Harwerth et al., J. Biol. Chem., 267, 15160-15167, 1992). In this paper we describe the effects of erbB-2 specific MAb administration on the tumorigenic growth of human erbB-2 transformed NIH3T3 cells implanted into athymic nude mice. Two antibodies, FWP51 and FSP77, inhibited the onset of tumour growth, while the administration of FRP5 and FSP16 did not affect tumour growth. In addition, administration of MAbs FWP51 and FSP77 led to a retardation in the growth of established tumours. Treatment was not curative in that tumours regrew within two weeks of the final treatment. The administration of a combination of MAbs FWP51 and FSP77 which react with two distinct regions on the erbB-2 molecule was more effective than treatment with either MAb alone. The two growth-inhibitory antibodies were also effective in the treatment of tumours established from SKOV3 cells, a human ovarian tumour cell line with high levels of the erbB-2 protein. The effect of the MAbs on the anchorage-independent growth of erbB-2 transformed cells and on erbB-2 receptor turnover was also measured.
Br J Cancer 1993 Dec
PMID:Monoclonal antibodies directed to the erbB-2 receptor inhibit in vivo tumour cell growth. 790 53

Indirect immunofluorescence analysis of sera from breast carcinoma patients whose tumors were characterized for overexpression of the c-erbB-2 oncoprotein (p185HER2) and for lympho-plasma cell infiltration, revealed no circulating antibodies specifically directed against the p185HER2 molecule in the 20 samples tested, whereas supernatants of B-cell clones, derived from Epstein-Barr virus-transformed peripheral blood lymphocytes from 10 of these patients, contained such antibodies in 6 of the 7 c-erbB-2- and lympho-plasma cell infiltration-positive cases. The antibodies contained in two of the positive supernatants immunoprecipitated a M(r) 185,000 molecule from oncoprotein-positive cell extracts that was identified as the oncoprotein in sequential immunoprecipitation experiments with anti-p185HER2 monoclonal antibodies. No cells producing antibodies with a similar reactivity were obtained from Epstein-Barr virus-transformed peripheral blood lymphocytes from breast carcinoma patients with p185HER2-negative tumors or from healthy donors. These data prove the existence of an antibody response specifically directed against the p185HER2 oncoprotein in breast carcinoma patients that may represent an important effector mechanism in the control of c-erbB-2-overexpressing tumors.
Cancer Res 1993 Dec 15
PMID:Antibody response against the c-erbB-2 oncoprotein in breast carcinoma patients. 790 96

Nineteen paraffin-embedded breast cancer tissue samples selected for long survival (more than 5 years) were analysed for detecting the amplification of the c-erbB-2 (Her-2/neu) oncogene by Polymerase Chain Reaction (PCR). Strong correlation was elucidated between c-erbB-2 amplification and survival; such correlation was also observed with histopathologic types and nuclear grading. Because of the similarity of the breast and ovarian cancer in the etiology of the diseases, amplification of c-erbB-2, c-myc and Ki-ras genes was examined in 32 ovarian carcinoma samples (stage I-IV). In ovarian carcinomas c-erbB-2 amplification occurred in 34% (11/32) of the fresh tumour samples, and correlation between amplification and clinical staging at P < 0.05 significance level was observed. Amplification of c-myc was detected in 9% (3/32) and none of the tumours showed amplification of Ki-ras.
Eur J Surg Oncol 1993 Dec
PMID:Oncogene patterns in breast and ovarian carcinomas. 790 45

The human erbB-2 gene encodes a receptor protein tyrosine kinase which has strong growth-promoting properties. Overexpression of erbB-2 is directly associated with tumor cell growth in vivo and in vitro. To investigate structural features which may contribute to expression, we isolated and sequenced a 3.65-kb 5' promoter fragment of the human erbB-2 gene. This 5' fragment contains an exceptionally high density of four Alu sequences. Other structural features include an A + T-rich region that causes DNA bending, as measured by anomalously slow migration in polyacrylamide gels. These structural features of the 5' region of erbB-2 may contribute to expression of the gene in different growth states.
Gene 1993 Dec 22
PMID:Structural features of the 5' region of the human erbB-2 gene. 790 74


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