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Expression of GCIP in transgenic mice decreases susceptibility to chemical hepatocarcinogenesis

Oncogene volume 25, pages 4207–4216 (2006)Cite this article

Abstract

Transcription factors with helix–loop–helix (HLH) motif play critical roles in controlling the expression of genes involved in lineage commitment, cell fate determination, proliferation, and tumorigenesis. To examine whether the newly identified HLH protein GCIP/CCNDBP1 modulates cell fate determination and plays a role in hepatocyte growth, proliferation, and hepatocarcinogenesis, we generated transgenic mice with human GCIP gene driven by a liver-specific albumin promoter. We demonstrated that in GCIP transgenic mice, the overall liver growth and regeneration occurred normally after liver injury induced by carbon tetrachloride (CCl4). In the diethylnitrosamine (DEN)-induced mouse hepatocarcinogenesis, we demonstrated that overexpression of GCIP in mouse liver suppressed DEN-induced hepatocarcinogenesis at an early stage of tumor development. The number of hepatic adenomas at 24 weeks was significantly lower or not detected in GCIP transgenic male mice compared to the control mice under the same treatment. Although GCIP has little inhibition on the number of hepatic tumors at later stages (40 weeks), hepatocellular tumors in GCIP transgenic mice are smaller and well-differentiated compared to the poorly differentiated tumors in wild-type mice. Furthermore, we demonstrate that GCIP functions as a transcriptional suppressor, regulates the expression of cyclin D1, and inhibits anchorage-independent cell growth and colony formation in HepG2 cells, suggesting a significant role of GCIP in tumor initiation and development.

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Acknowledgements

This work was supported partially from NIH Grants (5R01HL064792 and 1R01CA106479). We would like to thank members of the Liu laboratory and members of the Center for Cancer Biology and Nutrition for their comments and discussion.

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Authors and Affiliations

  1. Alkek Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, TX, USA

    W Ma, L J Stafford, C Yu, F Wang & M Liu

  2. Center for Cancer Biology and Nutrition, Texas A&M University System Health Science Center, Houston, TX, USA

    W Ma, L J Stafford, C Yu, F Wang & M Liu

  3. Department of Molecular and Cellular Medicine, Texas A&M University System Health Science Center, Houston, TX, USA

    W Ma, L J Stafford, C Yu, F Wang & M Liu

  4. The Graduate School of Biomedical Sciences, The University of Texas-Houston Health Science Center, Houston, TX, USA

    W Ma

  5. Department of Internal Medicine, The University of Texas-Houston Health Science Center, Houston, TX, USA

    X Xia & G LeSage

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Correspondence to M Liu.

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Ma, W., Xia, X., Stafford, L. et al. Expression of GCIP in transgenic mice decreases susceptibility to chemical hepatocarcinogenesis. Oncogene 25, 4207–4216 (2006). https://doi.org/10.1038/sj.onc.1209450

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