Abstract

Dr. Jirtle's group has recently demonstrated that the mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2r) gene is an important tumor suppressor in human and rat hepatocellular carcinoma (HCC). The proposed studies will focus on mouse model systems.
In Aim 1, HCCs from two carcinogen models will be analyzed to demonstrate that M6P/IGF2r gene lesions are present.
Aim 2 studies will evaluate the effect of M6P/IGF2r gene replacement in an HCC line that lacks a functional gene.
In Aim 3, a M6P/IGF2r transgenic that overexposes the gene will be evaluated for its sensitivity to liver carcinogenesis by two agents, diethylnitrosamine (DEN) and di[2-ethyl-hexyl]phthalate (DEHP). Finally, for Aim 4 studies, a transgenic mouse will be constructed with inducible knock-out of the M6P/IGF2r gene for evaluation in the carcinogenesis models.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES008823-05
Application #
6382218
Study Section
Metabolic Pathology Study Section (MEP)
Program Officer
Velazquez, Jose M
Project Start
1997-06-01
Project End
2002-05-31
Budget Start
2001-06-01
Budget End
2002-05-31
Support Year
5
Fiscal Year
2001
Total Cost
$290,510
Indirect Cost

  Institution

Name
Duke University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705

  Publications

Das, Radhika; Anderson, Nathan; Koran, Maryellen I et al. (2012) Convergent and divergent evolution of genomic imprinting in the marsupial Monodelphis domestica. BMC Genomics 13:394
Dolinoy, Dana C; Weinhouse, Caren; Jones, Tamara R et al. (2010) Variable histone modifications at the A(vy) metastable epiallele. Epigenetics 5:637-44
Bernal, Autumn J; Jirtle, Randy L (2010) Epigenomic disruption: the effects of early developmental exposures. Birth Defects Res A Clin Mol Teratol 88:938-44
Das, Radhika; Hampton, Daniel D; Jirtle, Randy L (2009) Imprinting evolution and human health. Mamm Genome 20:563-72
Dolinoy, Dana C (2008) The agouti mouse model: an epigenetic biosensor for nutritional and environmental alterations on the fetal epigenome. Nutr Rev 66 Suppl 1:S7-11
Dolinoy, Dana C; Jirtle, Randy L (2008) Environmental epigenomics in human health and disease. Environ Mol Mutagen 49:4-8
Dolinoy, Dana C; Das, Radhika; Weidman, Jennifer R et al. (2007) Metastable epialleles, imprinting, and the fetal origins of adult diseases. Pediatr Res 61:30R-37R
Dolinoy, Dana C (2007) Epigenetic gene regulation: early environmental exposures. Pharmacogenomics 8:5-10
Dolinoy, Dana C; Weidman, Jennifer R; Jirtle, Randy L (2007) Epigenetic gene regulation: linking early developmental environment to adult disease. Reprod Toxicol 23:297-307
Weidman, Jennifer R; Dolinoy, Dana C; Murphy, Susan K et al. (2007) Cancer susceptibility: epigenetic manifestation of environmental exposures. Cancer J 13:9-16

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