Analysis of oncogenes and tumor suppressor genes in human breast cancer.
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 estrogen-dependent proliferation.
Yamashita
H
H
Second Department of Surgery, Nagoya City University Medical School.
Kobayashi
S
S
Iwase
H
H
Itoh
Y
Y
Kuzushima
T
T
Iwata
H
H
Itoh
K
K
Naito
A
A
Yamashita
T
T
Masaoka
A
A
D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000401:mortality; D004273:DNA, Neoplasm / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000032:analysis; D015870:Gene Expression; D016161:Genes, Retinoblastoma; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D016259:Genes, myc; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009693:Nucleic Acid Hybridization; D009701:Nucleoside-Diphosphate Kinase; D009857:Oncogenes / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D016019:Survival Analysis; D014157:Transcription Factors / Q000032:analysis
D004273:DNA, Neoplasm; D066246:ErbB Receptors; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014157:Transcription Factors; C496444:FGF3 protein, human; C517938:NME1 protein, human