Estrogen receptor-alpha regulates SOCS-3 expression in human breast cancer cells.
The suppressor of cytokine signalling (SOCS) protein family negatively regulates cytokine action. In this study, we investigated the effects of estrogen (E2) on SOCS-3 expression in T47D and MCF-7 human breast cancer cells. Real-time PCR analysis of E2-treated T47D cells revealed a ligand and time-dependent increase in of SOCS-3 mRNA levels. Cloning of a 1.7 kb fragment of the human SOCS-3 5' flanking sequence, and subsequent analysis of potential transcription factor-binding sites identified an incomplete ERE motif located -1493 to -1489 upstream of the start site. Transient transfection of the cloned fragment in MCF-7 cells showed that both E2 and genistein treatment caused an increase in reporter gene activity, which was inhibited by co-treatment with ICI 182,780. Chromatin immunoprecipitation analysis revealed an E2 and time-dependent recruitment of ERalpha to the E2 responsive region of the human SOCS-3 promoter. In summary, this study shows that ERalpha directly regulates human SOCS-3 promoter activity in human breast cancer cells, thus modulating cytokine activity.
Matthews
Jason
J
Department of Biosciences at Novum, Karolinska Institutet, Novum, S-14157 Huddinge, Sweden. jason.matthews@biosci.ki.se
Almlöf
Tova
T
Kietz
Silke
S
Leers
Jörg
J
Gustafsson
Jan-Ake
JA
D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D047628:Estrogen Receptor alpha; D012097:Repressor Proteins; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors