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Methotrexate-induced senescence of human colon cancer cells depends on p53 acetylation, but not genomic aberrations

Dabrowska, Magdalenaa; Skoneczny, Marekc; Uram, Lukaszd; Rode, Wojciechb

doi: 10.1097/CAD.0000000000000731
PRECLINICAL REPORTS
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Human colon cancer C85 cell response to methotrexate has been documented previously to take on a form of reversible premature senescence. Seeking genomic aberrations encompassing candidate genes whose functional impairment could determine such a response to the drug, an array Comparative Genomic Hybridization method was applied, complemented by expression microarray data set searching. In the C85 cell genome, only short aberrations were identified, classified as focal chromosomal aberrations. 62% of the aberrant regions, selected by referral to normal human colon epithelium, were not carrying any gene. Out of the genes, subject to aberrations, 50% were protein-coding ones. Expression of those that could serve a signaling or a growth-regulatory function was found to be either downregulated or unchanged during C85 cell progression into methotrexate-induced senescence. Lack of extensive chromosomal instability in C85 cells is hypothesized to be attributed to the presence of the wild-type tumor suppressor p53 protein. Although two p53 protein isoforms were detected in C85 cells, stabilization and acetylation of the full-length p53 isoform were shown to underpin progression of the cells into premature senescence upon methotrexate treatment.

aLaboratory of Molecular Basis of Ageing

bNencki Institute of Experimental Biology, Warszawa

cDepartment of Genetics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw

dFaculty of Chemistry, Rzeszow University of Technology, Rzeszów, Poland

Correspondence to Magdalena Dabrowska, PhD, Laboratory of Molecular Basis of Ageing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093 Warszawa, Poland Tel: +48 225 892 250; fax: +48 228 225 342; e-mail: m.dabrowska@nencki.gov.pl

Received October 2, 2018

Accepted November 20, 2018

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