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Molecular cloning and characterization of a novel gene which is highly expressed in hepatocellular carcinoma

Oncogene volume 21, pages 4932–4943 (2002)Cite this article

Abstract

To gain new insight into the molecular mechanism underlying the pathogenesis of human primary hepatocellular carcinoma (HCC), we searched for HCC-specific molecules through screening genes that are differentially expressed between cancerous and noncancerous counterparts of liver and identified a novel HCC-associated gene, HCCA1 encoding a ∼80 kDa cytoplasmic protein that contains several proline-rich motifs likely for SH3-binding. HCCA1 transcript, albeit present in some adult tissues, is up-regulated selectively in HCC but not in other tumor cells. High expression of HCCA1 occurs as a late event frequently (89.2%) in HCCs and correlated significantly with the degree of tumor progression. When treated with antisense oligonucleotides to HCCA1, HCCA1 expression in HCC cells (HuH-7) was effectively suppressed and cell growth was down-regulated in a time- and dose-dependent manner. Furthermore, HuH-7 cells harboring the HCCA1 antisense expression clone displayed a remarkably reduced efficiency in colony formation. Together, these data strongly suggest that HCCA1 is a positive effector in cell proliferation and contributes to HCC carcinogenesis and progression. We believe that this protein will serve as a novel useful marker for HCC and is a potential target for pharmaceutical intervention of this malignant disease.

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Acknowledgements

This work was supported by grants from the State Key Basic Research Program (No. G1998051210) and the National Natural Science Foundation of China (No. 39830080, 39825114 and 30070833). We thank Dr Gang Pei for kindly providing the anchored and arbitrary primers, Dr Wenming Cong and Dr Yi Wang for helpful histopathological evaluation, and Dr Gengsheng Feng for reading and improving the manuscript.

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Author notes

  1. Jin-Zhang Zeng and Hong-Yang Wang: J-Z Zeng and H-Y Wang contributed equally to this work

Authors and Affiliations

  1. International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgical Institute, Secondary Military Medical University, Shanghai, 200438, P.R. China

    Jin-Zhang Zeng, Hong-Yang Wang, Zheng-Jun Chen & Meng-Chao Wu

  2. Max-Planck-Institut für Biochemie, Am Klopferspitz 18A, Martinsried, 82152, Germany

    Axel Ullrich

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  1. Jin-Zhang Zeng
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  2. Hong-Yang Wang
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Corresponding author

Correspondence to Hong-Yang Wang.

Additional information

The nucleotide sequence data reported in this paper will appear in the EMBL, GenBank and DDBJ nucleotide sequence databases under Accession number AF203474.

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Zeng, JZ., Wang, HY., Chen, ZJ. et al. Molecular cloning and characterization of a novel gene which is highly expressed in hepatocellular carcinoma. Oncogene 21, 4932–4943 (2002). https://doi.org/10.1038/sj.onc.1205652

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