Regulation of progesterone receptor messenger ribonucleic acid and protein levels in MCF-7 cells by estradiol: analysis of estrogen's effect on progesterone receptor synthesis and degradation.

Abstract:

:The human breast cancer cell line MCF-7 responds to estrogens with increased progesterone receptor (PR) levels. In this study, we use dense amino acid density shift analyses to address directly the question of whether estrogen increases PR levels in MCF-7 cells by altering rates of receptor synthesis and/or degradation. Using different concentrations of estradiol (E2), which achieve PR levels that are half-maximal (3 X 10(-11) M F2) or maximal (6 X 10(-11) M E2), we have done sucrose gradient density shift analyses using dense (15N, 13C, 2H) amino acid incorporation to study rates of PR synthesis and degradation. These studies reveal a nonlinear loss of preexisting normal density receptor with time. From kinetic modeling analyses, equivalent rates of degradation are estimated for PR whether maximal or half-maximal levels are maintained, indicating that the major effect of E2 on PR content is to increase the rate of PR synthesis while leaving the degradation rate unaltered. The E2-stimulated increase in PR protein is also associated with increased levels of PR mRNA, as demonstrated by the use of a human PR cDNA probe. These density shift data provide evidence that the increased PR levels after estrogen exposure in MCF-7 cells are the result of an increased rate of receptor synthesis, rather than modulation of the rate of receptor degradation.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Nardulli AM,Greene GL,O'Malley BW,Katzenellenbogen BS

doi

10.1210/endo-122-3-935

subject

Has Abstract

pub_date

1988-03-01 00:00:00

pages

935-44

issue

3

eissn

0013-7227

issn

1945-7170

journal_volume

122

pub_type

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