Abstract
An analytic strategy was followed to identify putative regulatory genes during the development of human hepatocellular carcinoma (HCC). This strategy employed a bioinformatics analysis that used a database search to identify genes, which are differentially expressed in human HCC and are also under cell cycle regulation. A novel cell cycle regulated gene (HURP) that is overexpressed in HCC was identified. Full-length cDNAs encoding the human and mouse HURP genes were isolated. They share 72 and 61% identity at the nucleotide level and amino-acid level, respectively. Endogenous levels of HURP mRNA were found to be tightly regulated during cell cycle progression as illustrated by its elevated expression in the G2/M phase of synchronized HeLa cells and in regenerating mouse liver after partial hepatectomy. Immunofluorescence studies revealed that hepatoma up-regulated protein (HURP) localizes to the spindle poles during mitosis. Overexpression of HURP in 293T cells resulted in an enhanced cell growth at low serum levels and at polyhema-based, anchorage-independent growth assay. Taken together, these results strongly suggest that HURP is a potential novel cell cycle regulator that may play a role in the carcinogenesis of human cancer cells.
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Acknowledgements
We thank Mien-Chie Hung (The University of Texas MD Anderson Cancer Center) for critical reading of the manuscript and Kuo-Ji Chen, Yu-Lun Liao, Min-Pey Ding, and Jung-Mao Hsu for their excellent technical assistance. We also thank Dr Anna F-Y Li for her assistance in patho-logical reading. This work was supported in part by grants from ADImmune Corporation, Program for Promoting Academic Excellence of Universities (89-B-FA22-2-4) and National Health Research Institutes (NHRI-EX90-9001-BL) to APT, MJF, and CKC, grant from the National Health Research Institutes to CFH, and grant from National Science Counsel (NSC-91-2323-B075-001) and Molecular Pathology core laboratory (National Yang Ming University) to CWC.
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Tsou, AP., Yang, CW., Huang, CY. et al. Identification of a novel cell cycle regulated gene, HURP, overexpressed in human hepatocellular carcinoma. Oncogene 22, 298–307 (2003). https://doi.org/10.1038/sj.onc.1206129
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DOI: https://doi.org/10.1038/sj.onc.1206129
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