Sukumar S, McKenzie K, Chen Y
Molecular Biology of Breast Cancer Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Mutat Res. 1995 Dec;333(1-2):37-44. doi: 10.1016/0027-5107(95)00129-8.
Rodent mammary tumors induced by chemical carcinogens have proven to be very useful in the genetic analysis of initiation, promotion and progression of mammary carcinogenesis. We are studying rat mammary carcinomas induced by the chemical carcinogen, N-nitroso-N-methylurea. The earliest genetic event observed in the mammary gland is the activation of Ha-ras oncogenes, which is followed by promotion of the initiated cells by hormones involved in puberty. Preferential amplification of the mutated Ha-ras allele, of PRAD-1 and IGF2, loss of expression of the mitogenic growth factor gene, MK, and mutation in the tumor suppressor gene, p53, are seen in the mammary tumors during tumor progression.
化学致癌物诱发的啮齿动物乳腺肿瘤已被证明在乳腺致癌作用的起始、促进和进展的遗传分析中非常有用。我们正在研究由化学致癌物N-亚硝基-N-甲基脲诱发的大鼠乳腺癌。在乳腺中观察到的最早的遗传事件是Ha-ras癌基因的激活，随后是青春期相关激素对起始细胞的促进作用。在肿瘤进展过程中，乳腺肿瘤中可见突变的Ha-ras等位基因、PRAD-1和IGF2的优先扩增、促有丝分裂生长因子基因MK的表达缺失以及肿瘤抑制基因p53的突变。
