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Long-term 17 alpha-ethinyl estradiol treatment decreases cyclin E and cdk2 expression, reduces cdk2 kinase activity and inhibits S phase entry in regenerating rat liver
Södertörn University, School of Life Sciences.
Södertörn University, School of Life Sciences.
Södertörn University, School of Life Sciences.ORCID iD: 0000-0001-9498-3033
2005 (English)In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 43, no 3, 478-484 p.Article in journal (Refereed) Published
Abstract [en]

Background/Aims: The synthetic estrogen 17 alpha-ethinyl estradiol (EE), a potent tumor promoter in rat liver, stimulates growth during short-term treatment but inhibits hepatocyte proliferation upon prolonged treatment. To identify the molecular targets of the mitoinhibitory effect of EE, the expression of proteins regulating G(1)- and S-progression were analyzed during the first cell cycle in EE-treated female Wistar rats. Methods: Long-term (60 days) EE treatment. Immunohistochemical staining for proliferation cell nuclear antigen (PCNA) to detect cells in S phase and quantification of mitosis. Western blot to monitor protein expression. Cdk2 kinase assay to examine histone H1 phosphorylation. Results: EE reduced the number of cells in S phase and mitosis by about 70%. Cyclin D-1 and D-3 were unaffected, while cdk4 was moderately decreased. Cyclin E and cdk2 were markedly decreased with concomitant marked reduction of cdk2 kinase activity. EE also decreased cyclin A and increased G(1) levels of p53 and p21. Conclusions: EE causes a cell cycle block before S-phase. The reduction of the cdk2 kinase activity, essential for G(1)/S-transition, might be involved in the cell cycle block. Also, EE treatment results in p53 activation and upregulation of the cdk inhibitor p21 that might contribute to the G(1) arrest.

Place, publisher, year, edition, pages
2005. Vol. 43, no 3, 478-484 p.
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:sh:diva-5877DOI: 10.1016/j.jhep.2005.02.050ISI: 000231481200016PubMedID: 16019103ScopusID: 2-s2.0-23444451236OAI: oai:DiVA.org:sh-5877DiVA: diva2:393875
Available from: 2011-02-01 Created: 2011-02-01 Last updated: 2016-10-04Bibliographically approved

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Koroxenidou, LenaOhlson, Lena C. E.Porsch Hällström, Inger
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