Linked Life Data

16109788

Source:http://linkedlifedata.com/resource/pubmed/id/16109788

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2005-10-17
pubmed:abstractText
Cancers, including that of the breast, are the result of multiple contributing factors including aberrant gene expression. Indeed, the CYP19 gene encoding P450 aromatase, the key enzyme for estrogen biosynthesis, is up-regulated in breast tumors predominantly via the cAMP-responsive gonad-type PII promoter, ultimately leading to increased intratumoral estrogen production and tumor growth. Thus, identifying the molecular factors involved in aromatase PII promoter regulation is essential for our understanding and treatment of the disease. Because we have previously shown activity of the murine aromatase PII promoter to be markedly up-regulated by GATA factors with respect to the gonads, we hypothesized that GATA factors are also key determinants of human PII promoter-driven aromatase transcription in breast tumors. We now show that GATA3 and GATA4 are indeed expressed in several breast cancer cells lines. Consistent with the cAMP dependence of the PII promoter, activation elicited by GATA3 or GATA4 alone and the striking synergism between GATA3 or GATA4 and the nuclear receptor liver receptor homolog (LRH)-1 was intimately linked to forskolin treatment or overexpression of protein kinase A (PKA) catalytic subunit. PKA-mediated phosphorylation increases the interaction between GATA3 and LRH-1 and the requirement for PKA in aromatase PII promoter stimulation involves at least three specific amino acid residues: GATA3 Ser308, GATA4 Ser261, and LRH-1 Ser469. Finally, we show that the human LRH-1 promoter is itself a target for GATA factors. Thus, taken together, our results suggest that GATA factors likely contribute to aberrant aromatase expression in breast tumors through two distinct, yet complementary mechanisms.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
146
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4905-16
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:16109788-Aromatase, pubmed-meshheading:16109788-Base Sequence, pubmed-meshheading:16109788-Breast Neoplasms, pubmed-meshheading:16109788-Cell Line, Tumor, pubmed-meshheading:16109788-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:16109788-DNA-Binding Proteins, pubmed-meshheading:16109788-Drug Synergism, pubmed-meshheading:16109788-Female, pubmed-meshheading:16109788-GATA3 Transcription Factor, pubmed-meshheading:16109788-GATA4 Transcription Factor, pubmed-meshheading:16109788-Humans, pubmed-meshheading:16109788-Molecular Sequence Data, pubmed-meshheading:16109788-Phosphorylation, pubmed-meshheading:16109788-Promoter Regions, Genetic, pubmed-meshheading:16109788-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:16109788-Transcription Factors, pubmed-meshheading:16109788-Transcriptional Activation
pubmed:year
2005
pubmed:articleTitle
Protein kinase A-dependent synergism between GATA factors and the nuclear receptor, liver receptor homolog-1, regulates human aromatase (CYP19) PII promoter activity in breast cancer cells.
pubmed:affiliation
Ontogeny and Reproduction Research Unit, T1-49, Centre Hospitalier de l'Université Research Centre, 2705 Laurier Boulevard, Ste-Foy, Quebec, Canada G1V 4G2.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't