Journal Article

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

J M Peters, T Aoyama, R C Cattley, U Nobumitsu, T Hashimoto and F J Gonzalez

in Carcinogenesis

Volume 19, issue 11, pages 1989-1994
Published in print November 1998 | ISSN: 0143-3334
Published online November 1998 | e-ISSN: 1460-2180 | DOI: https://dx.doi.org/10.1093/carcin/19.11.1989
Role of peroxisome proliferator-activated receptor alpha in altered cell cycle regulation in mouse liver.

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The mechanisms underlying peroxisome proliferator-induced hepatocarcinogenesis are unclear but are mediated by the peroxisome proliferator-activated receptor alpha (PPARalpha). To determine the role of PPARalpha 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 PPARalpha-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 PPARalpha-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 PPARalpha-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 PPARalpha. Thus PPARalpha-dependent alterations in cell cycle regulatory proteins induced by peroxisome proliferators are likely to contribute to the hepatocarcinogenicity of peroxisome proliferators.

Journal Article.  0 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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