Prolactin and estradiol utilize distinct mechanisms to increase serine-118 phosphorylation and decrease levels of estrogen receptor alpha in T47D breast cancer cells.
Potential interactions between prolactin (PRL) and estradiol (E2) in breast cancer cells were explored by examining the effect of PRL on estrogen receptor (ER) serine-118 phosphorylation, ER down-regulation, and E2-stimulated cell proliferation. Both E2 and PRL resulted in prolonged ERalpha serine-118 phosphorylation, but used different signaling pathways to achieve this end. Both hormones also decreased the amount of ERalpha, but the mechanisms were different: for E2, the decrease was rapid and resulted from proteasomic degradation, whereas for PRL the decrease was slow and resulted from an effect on levels of ERalpha mRNA. PRL alone had no effect on cell number, but enhanced the increase in number in response to E2. These results are the first to demonstrate similar effects of PRL and E2 on parameters considered key to E2's effects. This suggests heretofore unrecognized and potentially important interactions between these two hormones in the natural history of breast cancer.
Division of Biomedical Sciences, University of California, Riverside, CA 92521, USA.
Yenhao
Y
Chen
Kuangtzu
K
Huang
Kuanhui E
KE
Chen
Ameae M
AM
Walker
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D002452:Cell Count; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D010766:Phosphorylation; D011388:Prolactin / Q000378:metabolism* / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012694:Serine / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D047628:Estrogen Receptor alpha; D012694:Serine; D004958:Estradiol; D011388:Prolactin