Cell cycle dependent oscillatory expression of estrogen receptor-α links Pol II elongation to neoplastic transformation
Abstract
PvuII and XbaI polymorphisms at the estrogen receptor-α (ERα) intron 1 are associated with several estrogen-dependent pathologies including cancers. Here, we demonstrate that these SNPs map within a pausing site of Pol II elongation, a block that is cyclically released producing an oscillatory expression of ERα during cell division. The protoncogene c-MYB is part of this oscillator modulating the amplitude of ERα fluctuations in the presence of different SNP haplotypes. During breast cancer progression toward a hormone refractory phenotype, Pol II pausing contributes to turn off ERα synthesis highlighting the clinical relevance of the mechanism. Furthermore, the wide range of physio-pathological conditions associated with these SNPs, indicates this oscillator as a novel level of regulation of the hormonal signal throughout the body.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- July 2014
- DOI:
- 10.1073/pnas.1321750111
- Bibcode:
- 2014PNAS..111.9561V