Back to Search
Start Over
Transgenic CHD1L Expression in Mouse Induces Spontaneous Tumors
- Source :
- PLoS ONE, PLoS ONE, Vol 4, Iss 8, p e6727 (2009)
- Publication Year :
- 2009
- Publisher :
- Public Library of Science, 2009.
-
Abstract
- Background: Amplification of 1q21 is the most frequent genetic alteration in hepatocellular carcinoma (HCC), which was detected in 58-78% of primary HCC cases by comparative genomic hybridization (CGH). Using chromosome microdissection/ hybrid selection approach we recently isolated a candidate oncogene CHD1L from 1q21 region. Our previous study has demonstrated that CHD1L had strong oncogenic ability, which could be effectively suppressed by siRNA against CHD1L. The molecular mechanism of CHD1L in tumorigenesis has been associated with its role in promoting cell proliferation. Methodology/Principal Findings: To further investigate the in vivo oncogenic role of CHD1L, CHD1L ubiquitous-expression transgenic mouse model was generated. Spontaneous tumor formations were found in 10/41 (24.4%) transgenic mice, including 4 HCCs, but not in their 39 wild-type littermates. In addition, alcohol intoxication was used to induce hepatocyte pathological lesions and results found that overexpression of CHD1L in hepatocytes could promote tumor susceptibility in CHD1L-transgenic mice. To address the mechanism of CHD1L in promoting cell proliferation, DNA content between CHD1Ltransgenic and wildtype mouse embryo fibroblasts (MEFs) was compared by flow cytometry. Flow cytometry results found that CHD1L could facilitate DNA synthesis and G1/ S transition through the up-regulation of Cyclin A, Cyclin D1, Cyclin E, CDK2, and CDK4, and down-regulation of Rb, p27Kip1, and p53. Conclusion/Significance: Taken together, our data strongly support that CHD1L is a novel oncogene and plays an important role in HCC pathogenesis. © 2009 Chen et al.<br />published_or_final_version
- Subjects :
- Genetically modified mouse
Cyclin E
Genetics and Genomics/Animal Genetics
Cyclin A
Immunoblotting
lcsh:Medicine
Mice, Transgenic
Gastroenterology and Hepatology
medicine.disease_cause
Mice
Cyclin D1
Liver Neoplasms, Experimental
medicine
Animals
lcsh:Science
DNA-Binding Proteins - genetics - physiology
DNA Primers
DNA Helicases - genetics - physiology
Multidisciplinary
Cocarcinogenesis
biology
Oncogene
Base Sequence
Ethanol
Reverse Transcriptase Polymerase Chain Reaction
lcsh:R
Cell Cycle
DNA Helicases
Chromosome Mapping
Cell Cycle - physiology
Cell cycle
HCCS
Flow Cytometry
Molecular biology
DNA-Binding Proteins
Oncology
Cancer research
biology.protein
lcsh:Q
Liver Neoplasms, Experimental - chemically induced - genetics - pathology
Carcinogenesis
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 4
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....10855c34592b8ed4321e339339a5026b