Journal article

Cyclin E facilitates dysplastic hepatocytes to bypass G(1)/S checkpoint in hepatocarcinogenesis

Sharon Pok, Victoria Wen, Nicholas Shackel, Amber Alsop, Pawan Pyakurel, Aude Fahrer, Geoffrey C Farrell, Narci C Teoh

Journal of Gastroenterology and Hepatology | WILEY | Published : 2013

Abstract

BACKGROUND AND AIM: By array-comparative genomic hybridization, we demonstrated cyclin E as one of seven genes associated with hepatocellular carcinoma (HCC) development in Ku70 DNA repair-deficient mice. We therefore explored the hypothesis that during hepatocarcinogenesis, cyclin E kinase can overcome the inhibitory effects of p53 and establish whether abnormal miRNA(mi-R)-34, a co-regulator of cyclin E and p53, can account for their interactions as "drivers" of HCC. METHODS: Dysplastic hepatocytes (DNs) and HCCs were generated from diethylnitrosamine (DEN)-injected C57BL/6 male mice at 3-12 months. RESULTS: Cyclin E/cdk2 was barely expressed in normal liver, but was readily detected in dy..

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University of Melbourne Researchers

Grants

Awarded by Australian National Health and Medical Research Council's (NHMRC)


Awarded by NHMRC


Funding Acknowledgements

This work was supported by the Australian National Health and Medical Research Council's (NHMRC) project grant #418100, NHMRC program grant #358398, and The Canberra Hospital's Private Practice Trust Fund seed grant. The authors are grateful to Professor Philip Board, John Curtin School of Medical Research for his generous gift of GST-pi antibody and Derrick van Rooyen for assistance with CK-18 immunostaining. The authors also wish to thank Professor Elizabeth Musgrove from the Garvan Institute of Medical Research for advice with cyclin E kinase activity assays, Dr Deborah Heydet for her assistance with figures, and Boon Tin Chua for provision of the SoftGenetics' Mutation Surveyor (R) software in collaboration with the Singapore's A-Star Oncogenome project.