Kuperwasser C, Pinkas J, Hurlbut G D, Naber S P, Jerry D J
Program in Molecular and Cellular Biology, University of Massachusetts, Amherst 01003, USA.
Cancer Res. 2000 May 15;60(10):2723-9.
Proper function of the p53 tumor suppressor gene is critical for inhibiting tumor development in a broad spectrum of tissues. Although the mammary gland is highly susceptible to tumor formation, the functional status of p53 in the normal tissue had not been investigated. Therefore, expression, localization, and activity of p53 were examined in normal mammary tissues. High levels of p53 protein were found expressed in the cytoplasm of the ductal epithelium of the quiescent mammary gland. Ionizing radiation failed to recruit p53 to the nucleus, and p53-dependent responses were minimal. However, transient hormonal stimulation resulted in nuclear accumulation of p53, an induction of p21/WAF1, and a 5-fold increase in apoptosis after ionizing radiation. Therefore, the functional state of wild-type p53 in the mammary epithelium can be regulated by hormonal stimuli.
p53肿瘤抑制基因的正常功能对于抑制多种组织中的肿瘤发展至关重要。尽管乳腺极易发生肿瘤形成，但p53在正常组织中的功能状态尚未得到研究。因此，对正常乳腺组织中的p53表达、定位和活性进行了检测。发现静止乳腺导管上皮细胞质中表达高水平的p53蛋白。电离辐射未能将p53募集到细胞核，且p53依赖性反应极小。然而，短暂的激素刺激导致p53在细胞核中积累、p21/WAF1诱导以及电离辐射后细胞凋亡增加5倍。因此，乳腺上皮中野生型p53的功能状态可受激素刺激调节。
