2024-03-29T14:07:38Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1139552021-12-27T16:07:00Zcom_10261_134com_10261_1com_10261_41col_10261_387col_10261_294
00925njm 22002777a 4500
dc
Quiles, Ignacio
author
Millán-Ariño, Lluis
author
Subtil-Rodríguez, Alicia
author
Miñana, Belén
author
Spinedi, Nora
author
Ballaré, Cecilia
author
Beato, Miguel
author
Jordan, Albert
author
2009-06
Steroid hormone receptors act directly in the nucleus on the chromatin organization and transcriptional activity of several promoters. Furthermore, they have an indirect effect on cytoplasmic signal transduction pathways, including MAPK, impacting ultimately on gene expression. We are interested in distinguishing between the two modes of action of progesterone receptor (PR) on the control of gene expression and cell proliferation. For this, we have stably expressed, in PR-negative breast cancer cells, tagged forms of the PR isoform B mutated at regions involved either in DNA binding (DNA-binding domain) or in its ability to interact with the estrogen receptor and to activate the c-Src/MAPK/Erk/Msk cascade (estrogen receptor-interacting domain). Both mutants impair PR-mediated activation of a well-understood model promoter in response to progestin, as well as hormone-induced cell proliferation. Additional mutants affecting transactivation activity of PR (activation function 2) or a zinc-finger implicated in dimerization (D-box) have also been tested. Microarrays and gene expression experiments on these cell lines define the subsets of hormone-responsive genes regulated by different modes of action of PR isoform B, as well as genes in which the nuclear and nongenomic pathways cooperate. Correlation between CCND1 expression in the different cell lines and their ability to support cell proliferation confirms CCND1 as a key controller gene. Copyright © 2009 by The Endocrine Society.
Molecular Endocrinology 23(6): 809-826 (2009)
http://hdl.handle.net/10261/113955
10.1210/me.2008-0454
19299443
Mutational analysis of progesterone receptor functional domains in stable cell lines delineates sets of genes regulated by different mechanisms