Sex hormone-binding globulin antagonizes the anti-apoptotic effect of estradiol in breast cancer cells.
Sex hormone-binding globulin, the plasma carrier for sex steroids, inhibits the estradiol-induced proliferation of breast cancer cells. Estradiol induces cell proliferation triggering multiple mechanisms. Besides regulating growth factors, it activates Erk-1/-2, thus inhibiting apoptosis. In the present study, we investigated the effect of SHBG on estradiol-mediated anti-apoptotic effect in MCF-7 breast cancer cells. As expected, estradiol reduced the number of cells undergoing apoptosis. Although no modification of estradiol action was observed in cells treated contemporarily with estradiol and SHBG, pre-incubation with SHBG before estradiol treatment contrasted the anti-apoptotic effect completely. A mutant form of SHBG, lacking the O-linked oligosaccharide in Thr(7), displayed no such effect. Moreover, SHBG prevented the estradiol-induced phosphorylation of Erk-1/-2, whereas it had no effect on estradiol-induced transcription. Taken together, our observations suggest that the interaction of SHBG with MCF-7 cell membranes causes inhibition of the anti-apoptotic effect of estradiol which might account for SHBG's inhibitory effect on breast cancer cell growth.
Catalano
M G
MG
Department of Clinical Pathophysiology, University of Turin, Turin, Italy.
Frairia
R
R
Boccuzzi
G
G
Fortunati
N
N
D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006031:Glycosylation; D006801:Humans; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D012738:Sex Hormone-Binding Globulin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014158:Transcription, Genetic
D004965:Estrogen Antagonists; D012738:Sex Hormone-Binding Globulin; D004958:Estradiol; D048052:Mitogen-Activated Protein Kinase 3