Sex hormone-binding globulin selectively modulates estradiol-regulated genes in MCF-7 cells.
Human sex hormone-binding globulin inhibits the effects of estradiol on proliferation and apoptosis of breast cancer cells. We report here the effect of sex hormone-binding globulin on estradiol regulation of gene expression in MCF-7 breast cancer cells using a selected set of genes. Estradiol upregulates genes that are positive regulators of proliferation (e.g., bcl-2, c-fos, c-myc, cyclin D) or/and related to more aggressive form of breast cancer (e.g. BRCA-1, EGF-R) and downregulates two genes (c-jun and ERalpha). Sex hormone-binding globulin modulates only a selected group of estradiol-controlled genes (inhibiting upregulation of bcl-2, c-myc, EGF-R, PR, and downregulation of ERalpha), starting 48 hours after treatment. Our study demonstrates that in breast cancer cells, sex hormone-binding globulin is effective on few selected genes which are involved in cell growth and apoptosis or related to cell estrogen-dependence and that the protein regulation of estradiol effect is selected and specific. Sex hormone-binding globulin action in estrogen breast cancer cells is strongly associated to cell growth and estrogen-sensitivity.
Catalano
M G
MG
Department of Clinical Physiopathology, University of Turin, Turin, Italy.
Costantino
L
L
Frairia
R
R
Boccuzzi
G
G
Fortunati
N
N
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011388:Prolactin / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012738:Sex Hormone-Binding Globulin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D012738:Sex Hormone-Binding Globulin; D004958:Estradiol; D011388:Prolactin