Linked Life Data

20473858

Source:http://linkedlifedata.com/resource/pubmed/id/20473858

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-11-29
pubmed:abstractText
The DNA-damaging drug doxorubicin (Dox) induces cell senescence at concentrations significantly lower than those required for induction of apoptosis. At low Dox concentrations, tumor suppressor p53 is activated, which enhances the expression of p21(Waf1/Cip1) (p21). At high concentrations, Dox activates p53 leading to apoptosis without enhancing p21 expression. The underlying mechanisms and factors that govern the differential effects of Dox in inducing senescence and apoptosis are unclear. Here, we report that the DNA methyltransferase (DNMT) DNMT3a was upregulated by Dox especially at concentrations that induced apoptosis in HCT116 colorectal cancer cells, and this process was regulated by p53. Meanwhile, p21 expression was significantly upregulated at senescence-inducing concentrations and kept low on treatment with apoptosis-inducing concentrations of Dox. The differential expression of DNMT3a and p21 in response to Dox suggests that DNMT3a may be a key factor in switches between Dox-induced senescence and apoptosis. Moreover, when DNMT3a was silenced, treatment of HCT116 cells with apoptosis-inducing concentration of Dox increased the percentage of cells undergoing senescence, accompanied by upregulation of p21. Contrarily, senescence-inducing concentration of Dox promoted apoptosis rate, and p21 expression was repressed. Surprisingly, no changes in DNA methylation status at p21 promoter were detected at either ranges of Dox, although DNMT3a and HDAC1 were recruited to p21 promoter at apoptosis-inducing Dox concentration, where they were present in the same complex. Overall, these data demonstrate that DNMT3a impacts the expression of p21 and plays a role in determining the Dox-induced senescence and apoptosis in HCT116 cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1097-0215
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
128
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
551-61
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
DNMT3a plays a role in switches between doxorubicin-induced senescence and apoptosis of colorectal cancer cells.
pubmed:affiliation
The Institute of Genetics and Cytology, The Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University, Changchun, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't