Down-regulation of C/EBPalpha in breast cancer cells by hypoxia-estrogen combination is mainly due to hypoxia.

Abstract

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.

• Authors: Ramzi Seifeddine, Marie-Claude Fulchignoni-Lataud, Liliane Massaad-Massade
• Journal: Anticancer research (Anticancer Res) Vol. 29 Issue 4 Pg. 1227-31 (Apr 2009) ISSN: 0250-7005 [Print] Greece
• PMID: 19414368 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCAAT-Enhancer-Binding Proteins
• CEBPA protein, human
• Estrogens
• RNA, Messenger

Topics

• Breast Neoplasms (genetics, pathology)
• CCAAT-Enhancer-Binding Proteins (genetics, metabolism)
• Down-Regulation
• Estrogens (pharmacology)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Half-Life
• Humans
• Hypoxia (genetics)
• Immunoenzyme Techniques
• Promoter Regions, Genetic (genetics)
• RNA, Messenger (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Transcriptional Activation
• Tumor Cells, Cultured