ABSTRACT
Hepatocytes have a remarkable proliferative capacity, but are quiescent in normal
liver. Cell cycle activation in hepatocarcinogenesis can be directly triggered by
overexpression of single and combinations of genes or be initiated indirectly by compensatory
proliferation in response to liver injury. Work with transgenic and knockout mice
indicate that regardless of the initiating cause, constitutive hepatocyte proliferation
accompanied by genomic damage are essential factors for liver tumor development. The
carcinogenic process is best described as a continuum that involves unregulated hyperplasia,
dysplasia, and adenoma formation. The critical steps required for the transition from
regulated to constitutive hepatocyte proliferation and the mechanisms of genomic damage
in proliferating cells are being investigated. This knowledge should be directly applicable
to studies of human liver tumorigenesis.
KEY WORDS
transgenic mice - knockout mice - hepatocyte proliferation - genomic instability -
regeneration - dysplasia
