Cytoplasmic sequestration and functional repression of p53 in the mammary epithelium is reversed by hormonal treatment.

Abstract

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.