Linked Life Data

20221692

Source:http://linkedlifedata.com/resource/pubmed/id/20221692

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-12-3
pubmed:abstractText
A large proportion of breast cancers expresses the estrogen receptor alpha (ER?) and are dependent on estrogens for their proliferation and survival. The tumor suppressor TP53 encodes the p53 protein, an important mediator of the anti-proliferative and apoptotic effects of several treatments used for breast cancer. A significant proportions of breast tumors (20-30%) carry mutations in TP53 gene and these mutations are associated with poor survival and poor response to several types of chemotherapeutic treatments. While there is mounting evidence for functional interactions between p53 and ER? pathways in breast and other tissues, the impact of these interactions on response to chemotherapy and anti-hormone treatments remain largely unknown. Here, using estrogen-dependent breast cancer cell lines with different p53 status, we show that estrogens, through ER?, influence p53 protein levels and activities. Estrogen deprivation reduced, while estradiol increased p53 levels, in a time and dose-dependent manner. Both wild-type and endogenously expressed mutant p53 proteins were affected. This reduction in p53 protein levels resulted in reduced p53-dependent responses induced by DNA damage in p53 wild-type cells, lowering the capacity of doxorubicine to induce apoptosis. The p53 response appeared to be quantitatively but not qualitatively affected. These results suggest that ER? activity is required for a strong p53 response in estrogen-dependent breast cancer cells. These results are in line with previous observations that we made in a clinical series, where a larger effect of TP53 mutation status was found for patient survival in cases with progesterone receptor positive status, a marker of a functional ER? pathway. It would thus be important to further characterize the influence of ER? pathway on the predictive value of TP53 mutation status in specifically designed clinical trials, as it may open perspectives for improving breast cancer treatment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1573-7217
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
125
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35-42
pubmed:dateRevised
2011-4-21
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Estrogen levels act as a rheostat on p53 levels and modulate p53-dependent responses in breast cancer cell lines.
pubmed:affiliation
Molecular Carcinogenesis Group, International Agency for Research on Cancer, Lyon, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't