MAMMARY-TUMOR SUPPRESSION BY TRANSFORMING GROWTH-FACTOR-BETA-1 TRANSGENE EXPRESSION
MAMMARY-TUMOR SUPPRESSION BY TRANSFORMING GROWTH-FACTOR-BETA-1 TRANSGENE EXPRESSION
复制标题
DOI：
10.1073/pnas.92.10.4254
复制
发表时间：
1995-05-09
影响因子：
11.1
通讯作者：
MOSES, HL
中科院分区：
文献类型：
--
作者：
PIERCE, DF;GORSKA, AE;MOSES, HL
在细胞培养中，α 型转化生长因子 (TGF-α) 刺激上皮细胞生长，而 TGF-β1 会抑制这种刺激作用并抑制生长。在小鼠乳腺肿瘤病毒（MMTV）启动子/增强子的控制下过度表达 TGF-cu 的转基因小鼠表现出乳腺导管增生和乳腺癌的随机发展，这一过程可以通过施用化学致癌物 7,12-二甲基苯并[a]蒽来加速。 MR4TV-TGF-β1转基因小鼠表现出乳腺导管发育不全，并且不会发展为乳腺肿瘤。我们报道，在涉及生产同时携带 MMTV-TGF-β 1 和 MMTV-TGF-α 转基因小鼠的杂交实验中，乳腺肿瘤形成受到显着抑制，并且 MMTV-TGF-β 1 转基因小鼠对 7,12-二甲基苯并[a]蒽诱导的乳腺肿瘤形成具有抵抗力。这些数据表明体内过度表达TGF-β1可以显着抑制乳腺肿瘤的发展。
In cell culture, type alpha transforming growth factor (TGF-alpha) stimulates epithelial cell growth,whereas TGF-beta 1 overrides this stimulatory effect and is growth inhibitory. Transgenic mice that overexpress TGF-cu under control of the mouse mammary tumor virus (MMTV) promoter/enhancer exhibit mammary ductal hyperplasia and stochastic development of mammary carcinomas, a process that can be accelerated by administration of the chemical carcinogen 7,12-dimethylbenz[a]anthracene. MR4TV-TGF-beta 1 transgenic mice display mammary ductal hypoplasia and do not develop mammary tumors. We report that in crossbreeding experiments involving the production of mice carrying both the MMTV-TGF-beta 1 and MMTV-TGF-alpha transgenes, there is marked suppression of mammary tumor formation and that MMTV-TGF-beta 1 transgenic mice are resistant to 7,12-dimethylbenz [a] anthracene-induced mammary tumor formation. These data demonstrate that overexpression of TGF-beta 1 in vivo can markedly suppress mammary tumor development.