Hypoxia and estrogen co-operate to regulate gene expression in T-47D human breast cancer cells.

Abstract

Experimental and clinical studies have shown that both estrogen (E2) and hypoxia (H) are involved in tumor development and progression. A study was undertaken to determine whether these factors could interact to modulate gene expression using a microarray approach. We screened the transcript levels of over 8000 genes in the estrogen receptor (ERalpha) positive T-47D human breast cancer cell lines maintained at 21% O2 or 1% O2 with or without E2 co-treatment. Treatment by E2 or hypoxia alone altered the expression of 26 and 9 genes, respectively, whilst the expression of 31 genes was modulated by the H-E2 combination. The majority (21/31 genes) underwent a down-regulation. Microarray data was validated for 19 by quantitative real-time PCR and a good correlation noted (r2=0.8). Five out of these 19 genes were assayed for protein expression by Western blot. A correlation was also found between mRNA and protein levels. Statistical analysis showed that the gene expression modulation by the combined H and E2 treatment was additive in most cases, but for RasGRP2 and transferrin (TF) an antagonistic interaction was noted. The results demonstrate that hypoxic conditions and estrogen exposure interact to modulate the expression of a limited number of genes involved in cell growth and differentiation, angiogenesis, protein transport, metabolism and apoptosis.

• Authors: Ramzi Seifeddine, Anne Dreiem, Céline Tomkiewicz, Marie-Claude Fulchignoni-Lataud, Isabel Brito, Jean-Louis Danan, Vincent Favaudon, Robert Barouki, Liliane Massaad-Massade
• Journal: The Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 104 Issue 3-5 Pg. 169-79 (May 2007) ISSN: 0960-0760 [Print] England
• PMID: 17475478 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Estrogens
• Oxygen

Topics

• Breast Neoplasms (genetics, pathology)
• Cell Hypoxia (physiology)
• Estrogens (pharmacology)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Oligonucleotide Array Sequence Analysis
• Oxygen (pharmacology)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Cells, Cultured