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

Journal Article · Tue Mar 01 00:00:00 EST 1988 · Endocrinology; (United States)

DOI:https://doi.org/10.1210/endo-122-3-935· OSTI ID:5243927

Nardulli, A M; Greene, G L; O'Malley, B W; Katzenellenbogen, B S

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 (/sup 15/N, /sup 13/C, /sup 2/H) 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.

• Research Organization: Univ. of Illinois, Urbana (USA)
• OSTI ID: 5243927
• Journal Information: Endocrinology; (United States), Vol. 122:3
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ESTRADIOL
BIOCHEMICAL REACTION KINETICS
PROGESTERONE
RECEPTORS
BIOSYNTHESIS
AMINO ACIDS
CARBON 13
DEUTERIUM
MAMMARY GLANDS
MAN
MESSENGER-RNA
NEOPLASMS
NITROGEN 15
TRACER TECHNIQUES
TUMOR CELLS
ANIMAL CELLS
ANIMALS
BODY
CARBON ISOTOPES
CARBOXYLIC ACIDS
DISEASES
ESTRANES
ESTROGENS
EVEN-ODD NUCLEI
GLANDS
HORMONES
HYDROGEN ISOTOPES
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
KETONES
KINETICS
LIGHT NUCLEI
MAMMALS
MEMBRANE PROTEINS
NITROGEN ISOTOPES
NUCLEI
NUCLEIC ACIDS
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PREGNANES
PRIMATES
PROTEINS
REACTION KINETICS
RNA
STABLE ISOTOPES
STEROID HORMONES
STEROIDS
SYNTHESIS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques