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)

A panel of 73 samples, including 52 primary breast carcinomas, 10 normal breast tissues and 11 axillary lymph nodes, has been analysed for the presence of amplifications and gross structural alterations, in the oncogenes c-erbB-2, c-erbA, c-myc, N-myc, c-mos and c-Ha-ras. The tumours were also classified, graded and staged histopathologically and their DNA ploidy (42 samples) was determined by flow cytometry. Three breast cancer cell lines (MCF7, ZR-75-1 and T47D) were also included in the study. Amplification of c-erbB-2 was detected in 28% of the tumours, of which 91% had an increased steady-state level of c-erbB-2 mRNA. Amplification of c-erbA was found in 23% of tumours and was always associated with the amplification of c-erbB-2. Ten out of 12 (83%) tumours which had c-erbB-2 and c-erbA co-amplification had metastasised to axillary lymph nodes (P less than 0.006). However, the human thymidine kinase gene, which is present at the same chromosomal location as these two oncogenes (17q21-22), was amplified in only tw tumours. Amplification of c-myc was detected in 21% of the tumours studied, of which 82% (P less than 0.005) were of histopathological grade 3 and none were of grade 1. Flow cytometry showed that 90% (P less than 0.01) of the analysed tumours with c-erbB-2 and c-erbA co-amplification, and 70% (P less than 0.1) of those with c-myc amplification were DNA aneuploid. This study demonstrates the potential value of c-myc amplification in the assessment of the tumour grade, rather than metastatic potential; and of the co-amplification of c-erbB-2 and c-erbA as a strong indicator of metastatic potential, rather than tumour grade.
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PMID:c-erbB-2/c-erbA co-amplification indicative of lymph node metastasis, and c-myc amplification of high tumour grade, in human breast carcinoma. 257 68

We have analyzed genomic DNA sequences from 125 prospectively collected single unilateral primary breast carcinoma samples for the presence of alterations of c-myc, c-erbB-1, c-erbB-2, c-Ki-ras and c-Ha-ras protooncogenes. Amplification of the c-myc gene was found in 18% of the samples, and in one sample a non-germ line c-myc related DNA fragment or rearrangement was detected. We have found a significant association (P = 0.0010) between amplified c-myc gene and inflammatory carcinoma, a particularly aggressive breast cancer. The c-erbB-2 gene was amplified in 22% of the tumor samples and a rearrangement was observed once. Alteration of the c-erbB-2 gene was significantly linked to histological grade III tumors (P = 0.005) and the absence of estrogen and progesterone receptors (P = 0.036). No amplifications were observed for c-erbB-1, c-Ki-ras, and c-Ha-ras genes. About 40% of breast carcinomas contain either amplified c-myc or c-erbB-2 protooncogenes, whereas simultaneous amplification of both was seen in only one sample, suggesting the involvement of two distinct molecular mechanisms in breast cancer. Comparison of DNA from peripheral blood and tumor samples indicated loss of one c-Ha-ras allele in 29% of patients heterozygous for this polymorphism. A significant correlation (P = 0.016) between c-Ha-ras locus (11p14) allele loss and patient survival was found. These data suggest that 11p14 allelic loss plays a role in the evolution of human breast cancer, amplification of c-erbB-2 gene is associated with increasing stage of malignancy, and alteration of the c-myc gene in inflammatory breast carcinoma may contribute to the rapid progression of this human tumor subtype.
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PMID:Genetic alterations of c-myc, c-erbB-2, and c-Ha-ras protooncogenes and clinical associations in human breast carcinomas. 257 20

To investigate the relationship between oncogene activation and appearance of multidrug resistance (MDR) we transfected the human breast epithelial cell line MCF-10A, negative for the expression of the P-glycoprotein, with c-Ha-ras and/or c-erbB-2 oncogenes. The appearance of the MDR phenotype was then studied by evaluating mdr-1 mRNA expression, the presence of P-glycoprotein on the cell membrane and the onset of doxorubicin resistance, together with the effect of the reversing agent verapamil. We found that only MCF-10A transfected with both c-Ha-ras and c-erbB-2 oncogenes acquired the MDR phenotype.
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PMID:Induction of multidrug resistance (MDR) by transfection of MCF-10A cell line with c-Ha-ras and c-erbB-2 oncogenes. 792 21

MCF-10A is a spontaneously immortalized, non-transformed human mammary epithelial cell line. We have recently obtained MCF-10A clones (MCF-10A HE cells) that are transformed following over-expression of both a human point-mutated c-Ha-ras and the c-erbB-2 proto-oncogenes. Two isoforms of the cAMP-dependent protein kinase (cAK) have been described in mammalian cells. Enhanced levels of type-I cAK (cAKI) are generally found in tumor cells. To determine whether inhibition of cAKI expression may interfere with ras and erbB-2 oncogene-induced transformation of human mammary epithelial cells, we have tested the effects of 2 agents that specifically down-regulate cAKI, such as 8-chloro-cAMP and an anti-sense oligodeoxynucleotide targeted against the RI alpha regulatory subunit of cAKI on MCF-10A HE cells. Treatment of MCF-10A HE cells with 8-chloro-cAMP induces a dose-dependent growth inhibition under both monolayer and soft-agar growth conditions, that is correlated with an accumulation of MCF-10A HE cells in G0/G1 phases of the cell cycle and a reduction of the number of cells in S phase. In contrast, 8-chloro-cAMP has no effect on MCF-10A cell growth. Furthermore, 8-chloro-cAMP treatment of MCF-10A HE cells induces a 4- to 6-fold reduction in p185erbB-2 expression and brings p21ras expression to levels comparable to those found in MCF-10A cells. Treatment of MCF-10A HE cells with an RI alpha anti-sense oligodeoxynucleotide determines a comparable inhibition of both anchorage-dependent and anchorage-independent cell growth. Our results suggest that cAKI may act as a mediator of ras and erbB-2 oncogene action in human breast cells and that interference with cAKI action provides a potential tool for inhibiting the growth-promoting effects of these oncogenes.
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PMID:Down-regulation of RI alpha subunit of cAMP-dependent protein kinase induces growth inhibition of human mammary epithelial cells transformed by c-Ha-ras and c-erbB-2 proto-oncogenes. 809 73

Twenty-seven samples of pleomorphic salivary adenoma (PSA) were examined for expression and structure of c-myc, c-Ha-ras, c-erbB-2, c-sis oncogenes by RNA dot blot, DNA dot blot and Southern blot hybridization. Eighteen of 25 PSA showed 5.02 +/- 4.74 fold overexpression of c-myc oncogene, 6 of 19 PSA had 4.91 +/- 3.87 fold overexpression of c-Ha-ras oncogene. Two of 16 PSA were found to have overexpression of c-erbB-2 oncogene. In addition, 7 of 10 PSA and 1 of 9 PSA were detected to have c-myc and c-erbB-2 oncogene amplification respectively. However, no rearrangement, amplification or overexpression of c-sis gene was found. We also discussed various clinicopathological parameters of PSA, which however, had no significant correlation with expression of c-myc or c-Ha-ras oncogene. Our results indicate that activation of c-myc, c-Ha-ras and their combination may play an important role in the pathogenesis of PSA.
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PMID:Overexpression and amplification of c-myc and c-Ha-ras oncogenes in pleomorphic salivary adenoma. 838 70

Expression of oncogenes in gastric cancer tissue was evaluated with immunohistochemical staining methods using monoclonal antibodies to products of the oncogenes. Rates of expression in gastric cancer tissue were 50% for c-myc, 72% for c-erb B2, and 56% for c-Ha-ras oncogenes. Expression of these oncogenes in gastric cancer was not correlated with the histologic differentiation. The c-Ha-ras oncogene was positive in 19 of 26 cases with lymph node and/or distant metastasis: the positive rate was significantly higher than in cases without metastasis. Results suggest that c-Ha-ras oncogene is related to the prognosis of gastric cancer. The rate of expression of c-myc and c-Ha-ras oncogenes in gastric cancer tissues was higher in the DNA aneuploid group than in the DNA diploid group. Expression of c-myc and c-Ha-ras oncogenes correlated with other prognostic factors such as DNA ploidy pattern and metastasis. These oncogenes can be used to evaluate prognosis of gastric cancer patients.
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PMID:Expression of cellular oncogenes in human gastric carcinoma: c-myc, c-erb B2, and c-Ha-ras. 841 72

We established a novel cancer cell line (MAST) from the ascitic fluid of a metastatic infiltrating ductal carcinoma of the breast. The epithelial and neoplastic nature of the MAST cells was confirmed by ultrastructural analysis. The cell line was maintained as a monolayer with a doubling time of about 68 h, and it possessed an abnormal karyotype with a modal chromosome number of 60, a trisomy of chromosome 18 and other unidentified rearranged chromosomes. Among the markers consistently found in MAST metaphases, we noted a t(14; 14) and a very large subtelocentric, a large satellited acrocentric and a very large submetacentric chromosome with striking fluorescent bands. Immunoenzymatic assay demonstrated that the MAST cell line was positive for estrogen and progesterone receptors. The in vitro drug-sensitivity assay showed a marked resistance of the cell line to 5-fluorouracil and 4-hydroperoxycyclophosphamide and a moderate resistance to etoposide and 4'-epidoxorubicin. The molecular analysis showed a four-to sixfold amplification of the c-myc gene and no amplification or rearrangement of the int-2, c-erbB-2, c-Ha-ras, c-mos and hst-1 genes.
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PMID:A new cell line from human infiltrating ductal carcinoma of the breast: establishment and characterization. 860 77

Two human cancer cell lines (MA 2 and MA 3) were established from pleural effusions of infiltrating ductal carcinomas of the breast. The lines were maintained in continuous monolayer culture with doubling times of 70 (MA 2) and 78 (MA 3) hr for more than two years and possessed extensively rearranged abnormal karyo-types with modal chromosome number of 83 (MA 2) and 81 (MA 3) and DNA index values of 1.65 and 1.77, respectively. No amplifications or rearrangements were evident in the c-myc, int-2, c-erb B2, c-Ha-ras, or hst 1 genes in MA 2 and MA 3 cell lines. The clinical histories of the patients from whom the cell lines were derived are reported and compared with the results observed in the cell lines in vitro. The presence of CEA, CA 15-3, and MCA tumor markers observed in the primary tumor tissues was retained by the established cell lines. While the primary tumor tissues were ER+/PgR borderline+ (MA 2) and ER-/PgR+ (MA 3), the MA 2 line was ER+/PgR- and the MA 3 line remained ER-/PgR+. The MDR P-glycoprotein was not expressed either in primary tumor tissues or in the respective cell lines. High expression of cytokeratins 7, 18, and 19 was evident by immunohistochemical analysis in each cell line. whereas cytokeratins 8 and 17 were poorly or not at all expressed. The treatment history of the patients from whom the cell lines were derived involved CMF followed six months later by novantrone and cisplatin plus VP 16 (MA 2) and FEC followed four years later by CMF (MA 3). The chemosensitivity pattern assay of the cell lines indicated that the MA 2 line was sensitive to doxorubicin, cisplatin, and vinblastine, whereas the MA 3 line was sensitive to doxorubicin and cisplatin. The characteristics of these cell lines indicate them to be a good experimental model to investigate breast cancer biology and anticancer drug response.
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PMID:Establishment and characterization of two new cell lines derived from human metastatic breast carcinomas. 913 Dec 70

Capsaicin (CAP) has been known to inhibit some tumor development in vivo (J.J. Jang, S.H. Kim, T.K. Yun, Inhibitory effect of capsaicin on mouse lung tumor development, in vivo, J. Korean Med. Sci. 3 (1989) 49-53; J.J. Jang, K.J. Cho, Y.S. Lee, J.H. Bae, Different modifying responses of capsaicin in a wide-spectrum initiation model of F344 rat, J. Korean Med. 6 (1991) 31-36) [1,2] even though its mechanism of action is not well understood. The objectives of this study were to examine the effect of CAP on expression of tumor forming-related genes in a Korean stomach tumor cell, SNU-1. We used slot blot hybridization to investigate its effect on a wide spectrum of proto-oncogenes. It was found that CAP enhanced the transcripts of two proto-oncogenes (c-myc and c-Ha-ras) and tumor suppressor gene p53. While a low concentration of CAP (0.01 microM) did not significantly increase the level of p53 transcript in SNU-1, it did increase it by a factor of 3.5 at a 10 microM dose of CAP. Consequently, SNU-1 cells are sensitive to CAP in the overexpression of tumor suppressor gene, p53 and proto-oncogenes, c-myc and c-Ha-ras, but not those of c-erbB-2, c-jun and bcl-2 genes. Both cell death and DNA fragmentation were shown in SNU-1 cells with treatment of CAP. Our results suggest that CAP induces apoptotic cell death in human gastric cancer cells (SNU-1) in vitro which may be possibly mediated by the overexpression of p53 and/or c-myc genes. Because cell suicide is arguably the most potent natural defense against cancer, the correlation between the induction of apoptosis and the change of tumor forming-related gene expression after CAP treatment should be further studied in detail.
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PMID:Capsaicin can alter the expression of tumor forming-related genes which might be followed by induction of apoptosis of a Korean stomach cancer cell line, SNU-1. 946 Oct 43

Azatyrosine [L-beta-(5-hydroxy-2-pyridyl)-alanine] has the unique property of converting ras- or c-erbB-2 transformed phenotype to normal. The administration of azatyrosine also inhibits tumor formation in transgenic mice harboring the normal human c-Ha-ras which is mutated during treatment with various chemical carcinogens. To elucidate the molecular mechanism, we investigated how azatyrosine functions and what are its major targets. Azatyrosine functions downstream of ras; azatyrosine does not alter either the level of GTP-bound Ras or the total amount of Ras. Instead, azatyrosine inhibits the activation of c-Raf-1 kinase by oncogenic c-ErbB-2, resulting in inactivation of AP1. It is interesting that azatyrosine also restores the expression of the rhoB gene, the product of which regulates the formation of actin stress fibers. Azatyrosine is incorporated into cellular proteins to replace tyrosine. Several experiments indicate that replacement of tyrosine is likely to be a cause for its conversion of transformed phenotype to normal. To prove this hypothesis, we are attempting to develop a mutant of tyrosyl-tRNA synthetase that, unlike wild type, can aminoacylate azatyrosine more efficiently than can tyrosine.
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PMID:Azatyrosine. Mechanism of action for conversion of transformed phenotype to normal. 1066 9


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