Tesis doctoral de Alicia Subtil Rodríguez
Steroid hormone receptors regulate gene expression interacting with target dna sequences but also activating cytoplasmic signalling pathways. Using the human 11beta-hydroxysteroid dehydrogenase type 2 (11 -hsd2) gene as a model, we investigated the contribution of both effects on a human progesterone responsive promoter in breast cancer cells. Our results suggest two different mechanisms of hormone-induced pr recruitment to the 11 -hsd2 promoter: i,) direct pr binding to dna at the proximal promoter, abolished when pr contains a mutated dna binding domain (dbd); and ii,) stat5a-mediated recruitment of pr to the distal promoter region, impaired by a jak/stat pathway inhibitor. Therefore, coordination of pr transcriptional effects and cytoplasmic signalling activation, in particular jak/stat pathway, are critical to regulate progestins-induced endogenous 11 -hsd2 gene expression in breast cancer cells. This is not unique to this promoter, as the jak/stat inhibitor also alters expression of other progesterone-regulated genes. Additionally, we report rna polymerase ii tracking from the distal region upon pr and stat5a binding and we propose that this region works as hormone-dependent transcriptional enhancer.
Datos académicos de la tesis doctoral «Regulation of the 11beta-hydroxysteroid dehydrogenasetype 2 promoter by steroid hormones in breast cancer cells. convergence of progesterone receptor binding to dna and jak/stat pathway activation«
- Título de la tesis: Regulation of the 11beta-hydroxysteroid dehydrogenasetype 2 promoter by steroid hormones in breast cancer cells. convergence of progesterone receptor binding to dna and jak/stat pathway activation
- Autor: Alicia Subtil Rodríguez
- Universidad: Pompeu fabra
- Fecha de lectura de la tesis: 22/06/2007
Dirección y tribunal
- Director de la tesis
- Albert Jordan Vallés
- Tribunal
- Presidente del tribunal: ana Aranda iriarte
- jordi Bernués martínez (vocal)
- luciano Di croce (vocal)
- Fernández de mattos sílvia (vocal)