Role of peroxisome proliferator-activated receptor α in altered cell cycle regulation in mouse liver

Jeffrey Maurice Peters, Toshifumi Aoyama, Russell C. Cattley, Usuda Nobumitsu, Takashi Hashimoto, Frank J. Gonzalez

Research output: Contribution to journalArticle

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Abstract

The mechanisms underlying peroxisome proliferator-induced hepatocarcinogenesis are unclear but are mediated by the peroxisome proliferator-activated receptor α (PPARα). To determine the role of PPARα in the mechanisms of hepatocarcinogenesis, the effect of Wy-14,643 on expression patterns of acyl CoA oxidase (ACO) and proteins involved in cell proliferation in the PPARα-null mouse were evaluated. ACO, CDK-1, CDK-2, CDK-4, PCNA and c-myc proteins were significantly increased in wild-type mice fed Wy-14,643 for 5 weeks or 11 months, as compared with controls. This effect was not observed in Wy-14,643-treated PPARα-null mice. Expression patterns of cyclin B1, cyclin D, cyclin E and p53 were not different in any of the groups, mRNAs encoding CDK-1, CDK-4, cyclin D1 and c-myc were also increased in wild-type mice fed Wy-14,643 but not in PPARα-null mice. These results indicate that the increase in CDK-1, CDK-4 and c-myc may be caused by an increase in transcription that is mediated directly or indirectly by PPARα. Thus PPARα-dependent alterations in cell cycle regulatory proteins induced by peroxisome proliferators are likely to contribute to the hepatocarcinogenicity of peroxisome proliferators.

Original languageEnglish (US)
Pages (from-to)1989-1994
Number of pages6
JournalCarcinogenesis
Volume19
Issue number11
StatePublished - Nov 1 1998

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Peroxisome Proliferator-Activated Receptors
Cell Cycle
Peroxisome Proliferators
Liver
Acyl-CoA Oxidase
Proto-Oncogene Proteins c-myc
Cyclin D
Cyclin B1
Cyclin E
Cell Cycle Proteins
Cyclin D1
Proliferating Cell Nuclear Antigen
Cell Proliferation
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Peters, J. M., Aoyama, T., Cattley, R. C., Nobumitsu, U., Hashimoto, T., & Gonzalez, F. J. (1998). Role of peroxisome proliferator-activated receptor α in altered cell cycle regulation in mouse liver. Carcinogenesis, 19(11), 1989-1994.
Peters, Jeffrey Maurice ; Aoyama, Toshifumi ; Cattley, Russell C. ; Nobumitsu, Usuda ; Hashimoto, Takashi ; Gonzalez, Frank J. / Role of peroxisome proliferator-activated receptor α in altered cell cycle regulation in mouse liver. In: Carcinogenesis. 1998 ; Vol. 19, No. 11. pp. 1989-1994.
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Peters, JM, Aoyama, T, Cattley, RC, Nobumitsu, U, Hashimoto, T & Gonzalez, FJ 1998, 'Role of peroxisome proliferator-activated receptor α in altered cell cycle regulation in mouse liver', Carcinogenesis, vol. 19, no. 11, pp. 1989-1994.

Role of peroxisome proliferator-activated receptor α in altered cell cycle regulation in mouse liver. / Peters, Jeffrey Maurice; Aoyama, Toshifumi; Cattley, Russell C.; Nobumitsu, Usuda; Hashimoto, Takashi; Gonzalez, Frank J.

In: Carcinogenesis, Vol. 19, No. 11, 01.11.1998, p. 1989-1994.

Research output: Contribution to journalArticle

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Peters JM, Aoyama T, Cattley RC, Nobumitsu U, Hashimoto T, Gonzalez FJ. Role of peroxisome proliferator-activated receptor α in altered cell cycle regulation in mouse liver. Carcinogenesis. 1998 Nov 1;19(11):1989-1994.