Linked Life Data

16172191

Source:http://linkedlifedata.com/resource/pubmed/id/16172191

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2005-9-20
pubmed:abstractText
The breast and ovarian cancer susceptibility gene-1 (BRCA1) located on chromosome 17q21 encodes a tumor suppressor gene that functions, in part, as a caretaker gene in preserving chromosomal stability. The observation that most BRCA1 mutant breast cancers are hormone receptor negative has led some to question whether hormonal factors contribute to the etiology of BRCA1-mutant breast cancers. Nevertheless, the caretaker function of BRCA1 is a generic one and does not explain why BRCA1 mutations confer a specific risk for tumor types that are hormone-responsive or that hormonal factors contribute to the etiology, including those of the breast, uterus, cervix, and prostate. An accumulating body of research indicates that in addition to its well-established roles in regulation of the DNA damage response, the BRCA1 protein interacts with steroid hormone receptors (estrogen receptor (ER-alpha) and androgen receptor (AR)) and regulates their activity, inhibiting ER-alpha activity and stimulating AR activity. The ability of BRCA1 to regulate steroid hormone action is consistent with clinical-epidemiological research suggesting that: (i) hormonal factors contribute to breast cancer risk in BRCA1 mutation carriers; and (ii) the spectrum of risk-modifying effects of hormonal factors in BRCA1 carriers is not identical to that observed in the general population. These data suggest a model for BRCA1 carcinogenesis in which genomic instability leads to the initiation of cancerous cell clones, while loss of normal restraint on hormonal stimulation of mammary epithelial cell proliferation allows amplification of these pre-existing clones. Further research will be required to substantiate this hypothesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1351-0088
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
533-48
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
BRCA1 in hormonal carcinogenesis: basic and clinical research.
pubmed:affiliation
Department of Oncology, Lombardi Cancer Center, Georgetown University, 3970 Reservoir Road, NW, Washington, District of Columbia 20057, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural