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Department of Cell Biology Faculty
Miriam H. Feuerman, Ph.D.
Adjunct Associate Professor
Tel: (718) 270-1258 • Fax: (718) 270-3316
Genetic regulation of gene expression during liver regeneration and tumorigenesis
The normal adult liver has the unique ability to regenerate after poisoning, surgical resection or viral damage. However, repeated growth cycles as observed in chronic Hepatitis B Virus (HBV) or Hepatitis C Virus infection, can result in the failure of the normal controls on liver regeneration, leading to liver cancer. The alpha-fetoprotein (AFP) gene, an oncofetal antigen, is expressed in the developing fetus and under conditions of liver regeneration and tumorigenesis in the adult. The level of AFP gene expression during liver regeneration in mice is regulated by a genetically unlinked autosomal locus, Afr2. Inbred C57BL/6 mice express 8 to 10 fold less AFP during liver regeneration than wild type C3H/He mice. Lower AFP expression in regenerating liver reflects other regulatory processes, as C57BL/6 mice are less susceptible to liver carcinogenesis than C3H/He mice. The mechanisms that regulate growth may also regulate AFP gene expression making it an ideal surrogate marker to monitor the condition of the liver.
Pan, X., F.N. Hussain, J. Iqbal, M.H. Feuerman and M. M Hussain (2007). Inhibiting proteasomal degradation of microsomal triglyceride transfer protein prevents CCl4 induced steatosis. Journal of Biological Chemistry 282(23):17078-89
Jin, D.K., E.C. Anderson, E. Gilbert and M.H. Feuerman (2005). AFP gene expression acute diethylnitrosame intoxication is not Afr2 regulated. Cancer Letters 220 (2):211-220
Feuerman, M.H. (2002) Alpha-fetoprotein. Encyclopedia of Molecular Medicine. Editor: Thomas E. Creighton, EMBL. Editorial Board: C. Thomas Caskey, Michael R. Hayden, Haig H. Kakazian, Jr., George Klein, Hugo W. Moser, Anthony J. Pawson, Stuart H. Orkin, Bernard Roizman, R.V. Thakker, Hugh Watkins. Publisher John Wiley and Sons, New York
Jin, D.K., J. Vacher and M.H. Feuerman (1998). Alpha-fetoprotein Sequences Mediating Afr2 Regulation during Liver Regeneration. Proceedings of the National Academy of Science 95 (15): 8768-8772.
Jin, D.K. and M.H. Feuerman (1998). Chromosomal location of Afr2, regulator of alpha-fetoprotein gene expression during liver regeneration. Mammalian Genome. 9:256-258.