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

Cancer Res. 2000 May 15;60(10):2723-9.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chorionic Gonadotropin / pharmacology
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / metabolism
  • Cytoplasm / metabolism*
  • DNA Damage
  • Female
  • Genes, p53 / drug effects
  • Genes, p53 / physiology*
  • Genes, p53 / radiation effects
  • Gonadotropins, Equine / pharmacology
  • Mammary Glands, Animal / drug effects
  • Mammary Glands, Animal / metabolism*
  • Mammary Glands, Animal / radiation effects
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Placental Hormones / pharmacology*
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Cdkn1a protein, mouse
  • Chorionic Gonadotropin
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Gonadotropins, Equine
  • Placental Hormones
  • Tumor Suppressor Protein p53