Analysis of Oncogenes and Tumor Suppressor Genes in Human Breast Cancer

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Abstract

Oncogenes (c‐ erbB‐2, c‐ myc, and some genes linked to the 11q13 lesion), tumor suppressor genes (retinoblastoma gene, p53) and an antimetastatic gene ( nm23/nucleoside diphosphate kinase) play important roles in breast cancer progression. Amplification of c‐ erbB‐2, c‐ myc, and int‐2, and expression of RB, p53 (mutant), and NDP kinase were determined in 77 primary breast cancer specimens. nm23‐H1 allelic loss was also studied. c‐ erbB‐2 and c‐ myc amplification, loss of RB expression, p53(mutant) expression, and nm23‐H1 allelic loss were also found in non‐invasive carcinoma, int‐2 amplification was significantly correlated with lymph node status ( P=0.02) and a significant association was found between p53(mutant) expression and tumor size ( P=0.04). c‐ erbB‐2 amplification was strongly associated with disease‐free and overall survival in multivariate analysis ( P=0.002). All of the c‐ erbB‐2 amplified cases and all but one of the int‐2 amplified cases in node‐positive patients had relapsed within 2 years post resection. The cancer cells may acquire new proliferative pathways sequentially as a result of multiple genetic alterations which enable them to bypass the estrogendependent proliferation.

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Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor.

T. Yamamoto, S Ikawa, T. Akiyama … (2015)

A novel v-erb-B-related gene, c-erb-B-2, which has been identified in the human genome, maps to human chromosome 17 at q21 (ref. 40), and seems to encode a polypeptide with a kinase domain that is highly homologous with, but distinct from, that of the epidermal growth factor (EGF) receptor. The c-erb-B-2 gene is conserved in vertebrates and it has been suggested that the neu gene, detected in a series of rat neuro/glioblastomas, is, in fact, the rat c-erb-B-2 gene. Amplification of the c-erb-B-2 gene in a salivary adenocarcinoma and a gastric cancer cell line MKN-7 suggests that its over-expression is sometimes involved in the neoplastic process. To determine the nature of the c-erb-B-2 protein, we have now molecularly cloned complementary DNA for c-erb-B-2 messenger RNA prepared from MKN-7 cells. Its sequence shows that the c-erb-B-2 gene encodes a possible receptor protein and allows an analysis of the similarity of the protein to the EGF receptor and the neu product. As a consequence of chromosomal aberration in MKN-7 cells, a 4.6-kilobase (kb) normal transcript and a truncated 2.3-kb transcript of c-erb-B-2 are synthesized at elevated levels. The latter transcript presumably encodes only the extracellular domain of the putative receptor.