Linked Life Data

16860316

Source:http://linkedlifedata.com/resource/pubmed/id/16860316

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2006-9-4
pubmed:abstractText
The regulator of cell cycle progression, cyclin D1, is up-regulated in breast cancer cells; its expression is, in part, dependent on ERalpha signaling. However, many ERalpha-negative tumors and tumor cell lines (e.g., SKBR3) also show over-expression of cyclin D1. This suggests that, in addition to ERalpha signaling, cyclin D1 expression is under the control of other signaling pathways; these pathways may even be over-expressed in the ERalpha-negative cells. We previously noticed that both ERalpha-positive and -negative cell lines over-express BRCA1-IRIS mRNA and protein. Furthermore, the level of over-expression of BRCA1-IRIS in ERalpha-negative cell lines even exceeded its over-expression level in ERalpha-positive cell lines. In this study, we show that: (1) BRCA1-IRIS forms complex with two of the nuclear receptor co-activators, namely, SRC1 and SRC3 (AIB1) in an ERalpha-independent manner. (2) BRCA1-IRIS alone, or in connection with co-activators, is recruited to the cyclin D1 promoter through its binding to c-Jun/AP1 complex; this binding activates the cyclin D1 expression. (3) Over-expression of BRCA1-IRIS in breast cells over-activates JNK/c-Jun; this leads to the induction of cyclin D1 expression and cellular proliferation. (4) BRCA1-IRIS activation of JNK/c-Jun/AP1 appears to account for this, because in cells that were depleted from BRCA1-IRIS, JNK remained inactive. However, depletion of SRC1 or SRC3 instead reduced c-Jun expression. Our data suggest that this novel signaling pathway links BRCA1-IRIS to cellular proliferation through c-Jun/AP1 nuclear pathway; finally, this culminates in the increased expression of the cyclin D1 gene.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0014-4827
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
312
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3120-31
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16860316-BRCA1 Protein, pubmed-meshheading:16860316-Breast Neoplasms, pubmed-meshheading:16860316-Cell Proliferation, pubmed-meshheading:16860316-Chromosomal Proteins, Non-Histone, pubmed-meshheading:16860316-Cyclin D1, pubmed-meshheading:16860316-Enzyme Activation, pubmed-meshheading:16860316-Estrogen Receptor alpha, pubmed-meshheading:16860316-Exons, pubmed-meshheading:16860316-Gene Silencing, pubmed-meshheading:16860316-Humans, pubmed-meshheading:16860316-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:16860316-Promoter Regions, Genetic, pubmed-meshheading:16860316-Protein Binding, pubmed-meshheading:16860316-Proto-Oncogene Proteins c-jun, pubmed-meshheading:16860316-Proto-Oncogene Proteins c-myc, pubmed-meshheading:16860316-Trans-Activators, pubmed-meshheading:16860316-Transcription, Genetic, pubmed-meshheading:16860316-Transcription Factor AP-1, pubmed-meshheading:16860316-Transcriptional Activation, pubmed-meshheading:16860316-Tumor Cells, Cultured
pubmed:year
2006
pubmed:articleTitle
BRCA1-IRIS regulates cyclin D1 expression in breast cancer cells.
pubmed:affiliation
Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney St., Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't