Published in Cancer Detection and Prevention 1997; 21(1):36-43.

Gene Expressions and Activities of Protein Phosphatases 1α, 2a and 2c in Hepatocarcinogenesis and Regeneration After Partial Hepatectomy

Kunimi Kikuchi D.MedSC1, Kazuki Kitamura DSC1, Yasutaka Kakinoki DMedSC1,2, Koji Nakamura MS1, Shu-ichi Matsuzawa DSC1, Mostafa Saadat MS1, Yusuke Mizuno Dsc1

1Section of Biochemistry, Institute of Immunological Science; 2Third Department of Internal Medicine, Hokkaido University, Sapporo, Hokkaido, Japan

Address all correspondence and reprint requests to: Kunimi Kikuchi, D.Med.Sc., Section of Biochemistry, Institute of Immunological Science, Hokkaido University, Kita-15, Nishi-7, Kita- ku, Sapporo, Hokkaido 060, Japan.

ABSTRACT: The mRNA levels of protein phosphatases (PP) 1alpha, 2A, and 2C were determined both in hepatocarcinogenesis and in liver regeneration. In the precancerous stage and during regeneration, the mRNA levels of PP1alpha PP2A, and PP2C were markedly increased compared with those in normal livers. In primary hepatomas, all three of these mRNA levels were decreased to the control levels. In poorly differentiated hepatomas, however, only PP1alpha mRNA was specifically increased, in contrast to PP2A and PP2C, which were at the control levels or below. While PP1 activity in the non-nuclear fraction of partially hepatectomized livers was nearly constant, the activity in nuclei was increased about 2.5-fold over control levels at 12 h after partial hepatectomy, the time that corresponds to the G1 to S transition in the cell cycle of hepatocytes. On the other hand, PP2A activity in both fractions was nearly constant throughout. These results appear to suggest some involvement of protein phosphatases in regulation of hepatocyte proliferation.

KEY WORDS: protein phosphatase, mRNA, hepatocarcinogenesis, partial hepatectomy, hepatoma.