Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2009-5-27
pubmed:databankReference
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1944-9917
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
809-26
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:19299443-Cell Line, Tumor, pubmed-meshheading:19299443-Cell Proliferation, pubmed-meshheading:19299443-Cyclin D1, pubmed-meshheading:19299443-DNA Mutational Analysis, pubmed-meshheading:19299443-Enzyme Activation, pubmed-meshheading:19299443-Gene Expression Profiling, pubmed-meshheading:19299443-Gene Expression Regulation, Neoplastic, pubmed-meshheading:19299443-Humans, pubmed-meshheading:19299443-Kinetics, pubmed-meshheading:19299443-Models, Genetic, pubmed-meshheading:19299443-Mutant Proteins, pubmed-meshheading:19299443-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:19299443-Progestins, pubmed-meshheading:19299443-Promoter Regions, Genetic, pubmed-meshheading:19299443-Protein Binding, pubmed-meshheading:19299443-Protein Kinases, pubmed-meshheading:19299443-Protein Structure, Tertiary, pubmed-meshheading:19299443-RNA, Messenger, pubmed-meshheading:19299443-Receptors, Progesterone, pubmed-meshheading:19299443-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19299443-Signal Transduction, pubmed-meshheading:19299443-Time Factors
pubmed:year
2009
pubmed:articleTitle
Mutational analysis of progesterone receptor functional domains in stable cell lines delineates sets of genes regulated by different mechanisms.
pubmed:affiliation
Centre de Regulació Genòmica, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't