Silencing of Cited2 and Akap12 genes in radiation-induced rat osteosarcomas.
We have previously studied genomic copy number changes and global gene expression patterns in rat osteosarcomas (OS) induced by the bone-seeking alpha emitter (238)Pu by comparative genomic hybridization (CGH) and oligonucleotide microarray analyses, respectively. Among the previously identified genes that were down-regulated in radiation-induced rat OS tumors, Cited2 (Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2) and Akap12 (a kinase anchoring protein, also known as src-suppressed C-kinase substrate, SSeCKS) genes mapped to the most frequently lost regions on chromosome 1p. In the present study, relative copy number losses of Cited2 and Akap12 genes were observed in 8 of 15 (53%) and 10 of 15 (67%) tumors by quantitative PCR analysis. Loss of Cited2 and Akap12 in the tumors was confirmed at the levels of mRNA and protein expression by quantitative RT-PCR and immunoblot analyses, respectively. These results indicate that Cited2 and Akap12 are silenced in radiation-induced OS, and therefore are novel candidate tumor-suppressor genes of this tumor.
Daino
Kazuhiro
K
LCE/iRCM/DSV/CEA, 92265 Fontenay-aux-Roses Cedex, France. k_daino@nirs.go.jp
Roch-Lefevre
Sandrine
S
Ugolin
Nicolas
N
Altmeyer-Morel
Sandrine
S
Guilly
Marie-Noëlle
MN
Chevillard
Sylvie
S
D054758:A Kinase Anchor Proteins / Q000235:genetics*; D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000235:genetics*
D054758:A Kinase Anchor Proteins; C102361:Akap12 protein, rat; C517260:CITED2 protein, rat; D018797:Cell Cycle Proteins; D014157:Transcription Factors