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Recovery of Liver Mass without Proliferation of Hepatocytes after Partial Hepatectomy in Skp2-deficient Mice¹

Departments of Molecular and Cellular Biology [Y. A. M., K-I. N.] and Molecular Genetics [K. N., K-I. N.], Medical Institute of Bioregulation, Kyushu University, Fukuoka, Fukuoka 812-8582, and CREST, Japan Science and Technology Corporation, Kawaguchi, Saitama 332-0012 [Y. A. M., K. N., K-I. N.], Japan

The abundance of p27^Kip1, an inhibitor of cell proliferation, is determined by Skp2-dependent proteolysis, the deregulation of which is associated with cancer progression. Lack of Skp2 results in p27^Kip1 accumulation as well as enlargement and polyploidy of hepatocytes. The role of Skp2 in cell growth and proliferation was investigated in Skp2-deficient mice subjected to partial hepatectomy. Skp2^-/- mice exhibited restoration of liver mass without cell proliferation; rather, hepatocytes increased in size, an effect that was accompanied by increased polyploidy and p27^Kip1 accumulation. Lack of Skp2 thus impairs hepatocyte proliferation, which is compensated for by cellular enlargement, during liver regeneration.

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