Opposite effects of estrogen and the progestin R5020 on cell proliferation and GCDFP-15 expression in ZR-75-1 human breast cancer cells.
We have recently demonstrated that physiological concentrations of androgens caused a marked inhibition of basal and 17 beta-estradiol (E2)-induced cell growth in ZR-75-1 human breast cancer cells. Moreover, these steroids exert effects on GCDFP-15 (gross cystic disease fluid protein-15) expression that are opposite to their above-indicated actions on cell proliferation. The synthetic progestin R5020 (17.21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione), on the other hand, causes a potent inhibition of E2-induced ZR-75-1 cell growth. In order to further characterize the hormonal regulation of GCDFP-15 expression and to better understand the antagonism between progestin and estrogen action in breast cancer cells, we have studied the effect of R5020 on both GCDFP-15 expression and cell growth in ZR-75-1 cells. After a 10-day incubation, the 4-fold stimulatory effect of 1 nM E2 on cell growth was 60% decreased by maximal effective concentrations of R5020 (greater than 1 nM) while, in the absence of E2, R5020 had no effect. The mitogenic action of E2 was accompanied by a 75% inhibition of GCDFP-15 secretion while nanomolar concentrations of R5020 induced 1.4- and 5.2-fold increases in GCDFP-15 secretion in control and E2-treated ZR-75-1 cells, respectively. While E2 caused a marked inhibition of GCDFP-15 mRNA levels, R5020 induced a maximal 2- to 3-fold increase (above control) in GCDFP-15 mRNA accumulation in cells simultaneously incubated with E2.(ABSTRACT TRUNCATED AT 250 WORDS)
Dauvois
S
S
Medical Research Council Group in Molecular Endocrinology, CHUL Research Centre, Quebec, Canada.
Simard
J
J
Dumont
M
M
Haagensen
D E
DE
Labrie
F
F
D001053:Apolipoproteins; D053399:Apolipoproteins D; D001943:Breast Neoplasms / Q000473:pathology*; D002352:Carrier Proteins; D002455:Cell Division / Q000187:drug effects; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D005485:Flutamide / Q000031:analogs & derivatives / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006023:Glycoproteins; D006801:Humans; D026901:Membrane Transport Proteins; D015735:Mifepristone / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011397:Promegestone / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
C024328:APOD protein, human; D001053:Apolipoproteins; D053399:Apolipoproteins D; D002352:Carrier Proteins; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D009363:Neoplasm Proteins; C488892:PIP protein, human; C014290:hydroxyflutamide; D015735:Mifepristone; D004958:Estradiol; D005485:Flutamide; D011397:Promegestone