Oxytocin modulates estrogen receptor alpha expression and function in MCF7 human breast cancer cells.
Oxytocin (OT) inhibits the proliferation of MCF7 estrogen-dependent human breast cancer cells, via specific OT receptors (OTR). Besides this effect, we report that OT modulates the expression of estrogen receptor alpha (ERalpha) in MCF7 cells, both at mRNA and protein level. Since the first 24 h of OT treatment the ERalpha mRNA levels are down-regulated; in contrast, ERalpha protein expression decreases at a later time. The reduced number of ERalpha goes in parallel to a temporary increase in the binding affinity of these receptors as well as to a significant increase in their estradiol (E2)-induced transcription activity. The increase in both binding affinity and transcriptional activity of ERalpha likely balances the reduction in the number of ERalpha binding sites, ruling out the hypothesis that part of the OT contrasting effect on E2-induced cell proliferation could depend on the reduced E2 binding to MCF7 cells and supporting the hypothesis of an exclusively direct OT-antimitogenic effect. This is the first evidence that OT modulates the expression of ERalpha receptors in human neoplastic cells.
Department of Biomedical Sciences and Oncology, University of Turin, Turin, Italy.
Paola
P
Cassoni
Maria G
MG
Catalano
Anna
A
Sapino
Tiziana
T
Marrocco
Annamaria
A
Fazzari
Gianni
G
Bussolati
Nicoletta
N
Fortunati
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003593:Cytoplasm / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010121:Oxytocin / Q000494:pharmacology*; D011485:Protein Binding; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D004958:Estradiol; D010121:Oxytocin