Antagonism between estrogens and androgens on GCDFP-15 gene expression in ZR-75-1 cells and correlation between GCDFP-15 and estrogen as well as progesterone receptor expression in human breast cancer.
The androgen dihydrotestosterone (DHT) caused a maximal 65% inhibition of proliferation of the human breast cancer cells ZR-75-1 after a 10-day incubation period. The same treatment, on the other hand, stimulated by 25-fold the secretion of the breast marker protein GCDFP-15 (gross cystic disease fluid protein-15). The stimulatory effect of DHT on GCDFP-15 mRNA accumulation was already significant (1.6-fold, P less than 0.01) after a 12 h exposure and reached a maximal 25-fold increase after a 12-day incubation period. On the other hand, a 2-day exposure to 1 nM 17 beta-estradiol (E2) alone decreased by 60% GCDFP-15 mRNA levels while it completely blocked the 2.5-fold stimulation of GCDFP-15 secretion induced by concomitant incubation with DHT. Furthermore, a 10-day incubation with E2 increased by 4-fold the proliferation of ZR-75-1 cells whereas such treatment decreased by about 85% both GCDFP-15 mRNA accumulation and the secretion of the glycoprotein. The presence of GCDFP-15 mRNA in human breast cancer samples was restricted to estrogen receptor positive tumors and was significantly correlated with progesterone receptor expression.
Dumont
M
M
Medical Research Council Group in Molecular Endocrinology, Laval University Medical Centre, Quebec, Canada.
Dauvois
S
S
Simard
J
J
Garcia
T
T
Schachter
B
B
Labrie
F
F
D001053:Apolipoproteins; D053399:Apolipoproteins D; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms; D002352:Carrier Proteins; D002460:Cell Line; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006023:Glycoproteins; D006801:Humans; D007700:Kinetics; D026901:Membrane Transport Proteins; D009363:Neoplasm Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism*
C024328:APOD protein, human; D001053:Apolipoproteins; D053399:Apolipoproteins D; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D009363:Neoplasm Proteins; C488892:PIP protein, human; D012333:RNA, Messenger; D013196:Dihydrotestosterone; D004958:Estradiol