Transcriptomic profiling of radiation-resistant or -sensitive human colorectal cancer cells : Acute effects of a single X-radiation dose

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TypeArticle
Journal titleInt.J.Oncol.
Volume30
Issue6
Pages13691380; # of pages: 12
Subjectanalysis; Apoptosis; Blotting,Western; Canada; cell; Cell Line; Cell Line,Tumor; CELLS; Colorectal Neoplasms; DNA; Down-Regulation; GENE; Gene Expression Profiling; Gene Expression Regulation; Genes; genetics; Human; Humans; MODEL; Oligonucleotide Array Sequence Analysis; PATHWAY; PATHWAYS; Phenotype; radiation effects; Radiation Tolerance; Rna; X-Rays
AbstractWe previously isolated several clones that were closely-related genetically from a human colorectal tumor (HCT116) cell line. These clones displayed significantly different X-radiation response phenotypes. In this paper, we investigated how a single dose of X-radiation modulated the transcriptomic profiles of either the radiation-resistant (HCT116Clone2_XRR) or the radiation-sensitive (HCT116CloneK_XRS) clone when each was compared to a reference clone, HCT116Clone10_control. The latter represented a control clone that displayed a similar X-radiation response as the parental HCT116 cells. Pooled RNAs were obtained from HCT116Clone2_XRR, HCT116CloneK_XRS or HCT116Clone10_control cells either before or at 10 min, 6 or 24 h after treatment with 4-Gy X-radiation. Transcriptomic profiles were assessed by cDNA microarrays. At least three independent experiments were carried out for each time point and statistical analysis was performed by paired t-test (p<0.05). From 19,200 genes/ESTs examined, we identified only 120 genes/ESTs that were differentially expressed at any one of these four time points. Interestingly, different patterns of gene modulation were observed between the radiation-sensitive and radiation-resistant clones. However, the fold changes of gene modulation were generally small (2-3 fold). Surprisingly, only 12.7% of 79 genes involved in DNA damage sensor/repair and cell cycle and between 2.6 and 9.2% of 76 genes involved in apoptosis, were significantly modulated in these early time points following irradiation. By comparison, up to 10% of 40 known housekeeping genes were differentially expressed. Thus in our experimental model, we were able to detect the up-regulation or down-regulation of mostly novel genes and/or pathways in the acute period (up to 24 h) following a single dose of 4-Gy X-radiation
Publication date
LanguageEnglish
AffiliationNational Research Council Canada; NRC Institute for Biological Sciences
Peer reviewedNo
NRC numberNG2007
NPARC number9380119
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Record identifier25bd6148-7520-463a-a85d-eed432b75a47
Record created2009-07-10
Record modified2016-05-09
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