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[Cancer Research 60, 2723-2729, May 15, 2000]
© 2000 American Association for Cancer Research

Molecular Biology and Genetics

Cytoplasmic Sequestration and Functional Repression of p53 in the Mammary Epithelium Is Reversed by Hormonal Treatment1

Charlotte Kuperwasser, Jan Pinkas, Gregory D. Hurlbut, Stephen P. Naber and D. Joseph Jerry2

Program in Molecular and Cellular Biology [C. K., J. P., D. J. J.], and Department of Veterinary and Animal Sciences [G. D. H., D. J. J.], University of Massachusetts, Amherst, Massachusetts 01003, and Department of Pathology; Baystate Medical Center, Springfield, Massachusetts 01199 [S. P. N.]

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.




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