Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
Reprod Biol Endocrinol. 2010 Jun 21;8:69. doi: 10.1186/1477-7827-8-69.
Inhibin is a tumor-suppressor and activin antagonist. Inhibin-deficient mice develop gonadal tumors and a cachexia wasting syndrome due to enhanced activin signaling. Because activins signal through SMAD2 and SMAD3 in vitro and loss of SMAD3 attenuates ovarian tumor development in inhibin-deficient females, we sought to determine the role of SMAD2 in the development of ovarian tumors originating from the granulosa cell lineage.
Using an inhibin alpha null mouse model and a conditional knockout strategy, double conditional knockout mice of Smad2 and inhibin alpha were generated in the current study. The survival rate and development of gonadal tumors and the accompanying cachexia wasting syndrome were monitored.
Nearly identical to the controls, the Smad2 and inhibin alpha double knockout mice succumbed to weight loss, aggressive tumor progression, and death. Furthermore, elevated activin levels and activin-induced pathologies in the liver and stomach characteristic of inhibin deficiency were also observed in these mice. Our results indicate that SMAD2 ablation does not protect inhibin-deficient females from the development of ovarian tumors or the cachexia wasting syndrome.
SMAD2 is not required for mediating tumorigenic signals of activin in ovarian tumor development caused by loss of inhibin.
抑制素是一种肿瘤抑制因子和激活素拮抗剂。抑制素缺乏的小鼠由于激活素信号增强而发展为性腺肿瘤和恶病质消耗综合征。因为激活素在体外通过 SMAD2 和 SMAD3 信号转导，并且 SMAD3 的缺失减弱了抑制素缺乏雌性小鼠的卵巢肿瘤发展，所以我们试图确定 SMAD2 在起源于颗粒细胞谱系的卵巢肿瘤发展中的作用。
本研究使用抑制素 α 缺失小鼠模型和条件性敲除策略，生成了 Smad2 和抑制素 α 的双条件性敲除小鼠。监测了生存率和性腺肿瘤的发展以及伴随的恶病质消耗综合征。
与对照组几乎相同，Smad2 和抑制素 α 双敲除小鼠因体重减轻、侵袭性肿瘤进展和死亡而死亡。此外，还观察到这些小鼠中存在升高的激活素水平以及激活素诱导的肝脏和胃中的病理变化，这些变化是抑制素缺乏的特征。我们的结果表明，SMAD2 的缺失不能保护抑制素缺乏的雌性免于发生卵巢肿瘤或恶病质消耗综合征。
SMAD2 不参与介导由抑制素缺失引起的激活素在卵巢肿瘤发展中的致癌信号。
