DNA Copy Number Aberrations and Disruption of the p16lnk4a/Rb Pathway in Radiation-Induced and Spontaneous Rat Mammary Carcinomas

Chromosomal amplifications and deletions are thought to be important events in spontaneous and radiation-induced carcinogenesis. To clarify how ionizing radiation induces mammary carcinogenesis, we characterized genomic copy number aberrations for γ-ray-induced rat mammary carcinomas using microarra...

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Veröffentlicht in:Radiation research 2010-08, Vol.174 (2), p.206-215
Hauptverfasser: Iizuka, Daisuke, Imaoka, Tatsuhiko, Takabatake, Takashi, Nishimura, Mayumi, Kakinuma, Shizuko, Nishimura, Yukiko, Shimada, Yoshiya
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Sprache:eng
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Zusammenfassung:Chromosomal amplifications and deletions are thought to be important events in spontaneous and radiation-induced carcinogenesis. To clarify how ionizing radiation induces mammary carcinogenesis, we characterized genomic copy number aberrations for γ-ray-induced rat mammary carcinomas using microarray-based comparative genomic hybridization. We examined 14 carcinomas induced by γ radiation (2 Gy) and found 26 aberrations, including trisomies of chromosomes 4 and 10 for three and one carcinomas, respectively, an amplification of the chromosomal region Iql2 in two carcinomas, and deletions of the chromosomal regions 3q35q36,5q32 and 7qll in two, two and four carcinomas, respectively. These aberrations were not observed in seven spontaneous mammary carcinomas. The expression of pl6Ink4a and pl9Arf, which are located in the chromosomal region 5q32, was always up-regulated except for a carcinoma with a homozygous deletion of region 5q32. The up-regulation was not accounted for by gene mutations or promoter hypomethylation.However, the amounts of Rb and its mRNA were down-regulated in these carcinomas, indicating a disruption of the pl6Ink4a/Rb pathway. This is the first report of array CGH analysis for radiation-induced mammary tumors, which reveals that they show distinct DNA copy number aberration patterns that are different from those of spontaneous tumors and those reported previously for Chemically induced tumors.
ISSN:0033-7587
1938-5404