Down-regulation of C/EBPalpha in breast cancer cells by hypoxia-estrogen combination is mainly due to hypoxia
Seifeddine, R.; Fulchignoni-Lataud, M.-C.; Massaad-Massade, L.
Anticancer Research 29(4): 1227-1231
2009
ISSN/ISBN: 0250-7005 PMID: 19414368 Document Number: 628484
CCAAT/enhancer binding protein-alpha (C/EBPalpha) is involved in the control of cell differentiation and proliferation. It has been previously shown that hypoxia (H) down-regulates C/EBPalpha in breast cancer cells; here the effect of estrogen (E(2)) during H on C/EBPalpha in T-47D cell line was examined. By quantitative RT-PCR the C/EBPalpha mRNA stability was analyzed at 21% O(2) and 1% O(2) under E(2). The H-E(2) combination but not E(2) alone reduced the half-life of the C/EBPalpha mRNA. C/EBPalpha promoter activity studies covering -576 bp do not show any effect of E(2); a significant decrease of C/EBPalpha transcriptional activity was found in the C/EBPalpha promoter between -576/416 bp as previously observed when cells were treated with hypoxia alone. By immunocytochemistry, H-E(2) combination alters the cellular distribution of C/EBPalpha in T-47D cells and locates this protein mainly at the cytosol. Therefore, the observed down-regulation of C/EBPalpha by the H-E(2) combination in T-47D cells is mainly due to the hypoxia effect.