Related Experiment Video
Updated: Jun 19, 2026

A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
Published on: May 3, 2021
Silencing of Cited2 and Akap12 genes in radiation-induced rat osteosarcomas
Kazuhiro Daino1, Sandrine Roch-Lefevre, Nicolas Ugolin
1LCE/iRCM/DSV/CEA, 92265 Fontenay-aux-Roses Cedex, France. k_daino@nirs.go.jp
Abstract:
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.
Insights
Radiation-induced osteosarcoma (OS) in rats shows down-regulation of Cited2 and Akap12 genes. These genes are identified as novel candidate tumor-suppressor genes in this specific cancer.
Area of Science:
- Oncology
- Genetics
- Radiation Biology
Background:
- Osteosarcoma (OS) is a bone cancer.
- Radiation exposure can induce OS.
- Previous studies identified gene expression changes in radiation-induced OS.
Purpose of the Study:
- Investigate the role of Cited2 and Akap12 genes in radiation-induced rat osteosarcoma.
- Determine if copy number losses correlate with gene silencing.
- Evaluate Cited2 and Akap12 as potential tumor suppressors.
Main Methods:
- Quantitative PCR (qPCR) to assess gene copy number.
- Quantitative RT-PCR to measure mRNA expression levels.
- Immunoblot analysis to detect protein expression.
Main Results:
- Cited2 gene copy number loss observed in 53% of tumors.
- Akap12 gene copy number loss observed in 67% of tumors.
- Down-regulation of Cited2 and Akap12 mRNA and protein expression confirmed.
Conclusions:
- Cited2 and Akap12 genes are frequently silenced in radiation-induced osteosarcoma.
- These genes represent novel candidate tumor-suppressor genes for this cancer type.
Related Concept Videos
The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Abnormal Proliferation
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Rous Sarcoma Virus (RSV) and Cancer
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...

