DEHYDROEPIANDROSTERONE AND ANDROST-5-ENE-3-BETA, 17-BETA-DIOL IN HUMAN MAMMARY-CANCER CYTOSOLIC AND NUCLEAR COMPARTMENTS AND THEIR RELATIONSHIP TO ESTROGEN-RECEPTOR

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (10) , 3815-3820
Abstract
Dehydroepiandrosterone (DHEA) and 5-androstene-3.beta.,17.beta.-diol (ADIOL) were determined by radioimmunoassay in human primary mammary cancer cytosol preparations. The range and means .+-. SD (ng/g wet wt, of tissue) in individual tumors were: DHEA, 12.3 .+-. 14.4 n [sample size] = 34; and ADIOL, 2.7 .+-. 2.1, n = 43. In 23 tumors in which both steroids were measured in the same extract, they were significantly correlated. In these tumors the ratio of ADIOL to DHEA was lower in estrogen receptor-(ERC)-negative than in ERC-positive tumors, but this difference was not significant. The ratio of ADIOL to DHEA was 5-fold higher in purified nuclei obtained from pooled primary mammary cancer tissue compared to that in the cytosol. DHEA was present in the cytosol of tumors from premenopausal women in significantly higher concentrations than in cytosols of postmenopausal women [0.73 .+-. 0.49 ng/mg cytosol protein (n = 14) vs. 0.35 .+-. 0.35 (n = 19); P < 0.02], whereas the concentrations of ADIOL were similar [0.12 .+-. 0.09 ng/mg cytosol protein (n = 18) and 0.10 .+-. 0.11 (n = 25), for pre- and postmenopausal women, respectively]. In ERC-positive tumors, there was a negative correlation between ERC concentration and cytosol ADIOL levels in premenopausal (r = -0.46, n = 10) and postmenopausal (r = -0.24; n = 20) subjects and also DHEA levels in postmenopausal women only (r = -0.30; n = 12). None of these correlations reached statistical significance. In view of the known high affinity of ADIOL for ERC (Kd .apprxeq. 6 nM) and its estrogen-like activity in vivo, the concentration of ADIOL in the tumor cytosols apparently is sufficiently high to translocate ERC and provoke an estrogen response.