Yoshidome K, Shibata M A, Maroulakou I G, Liu M L, Jorcyk C L, Gold L G, Welch V N, Green J E
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Building 41, Room C629, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Int J Oncol. 1998 Feb;12(2):449-53.
We have generated a transgenic mouse model in which female mice develop ductal mammary adenocarcinomas and male mice develop prostatic adenocarcinomas by using a transgene containing the hormone-responsive rat prostatic steroid binding protein 5' flanking region C3(1) fused to the simian virus 40 (SV40) large T antigen. We have identified some genetic alterations during mammary and prostate tumor progression: (i) p53 is functionally inactivated during mammary cancer development without p53 mutations; (ii) Alterations in apoptosis during mammary tumor progression are p53 and bcl-2 independent; (iii) Ha-ras mutations occur early in the development of prostate cancer. This unique animal model offers the opportunity to study multistep tumorigenesis in these organs.
我们通过使用一个包含与猿猴病毒40（SV40）大T抗原融合的激素反应性大鼠前列腺类固醇结合蛋白5'侧翼区域C3(1)的转基因，构建了一种转基因小鼠模型，其中雌性小鼠会发生乳腺导管腺癌，雄性小鼠会发生前列腺腺癌。我们已经在乳腺和前列腺肿瘤进展过程中鉴定出一些基因改变：（i）在乳腺癌发展过程中p53功能失活，但无p53突变；（ii）乳腺肿瘤进展过程中细胞凋亡的改变与p53和bcl-2无关；（iii）Ha-ras突变在前列腺癌发展早期出现。这种独特的动物模型为研究这些器官中的多步骤肿瘤发生提供了机会。
