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  • Oncogenomics
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Molecular cloning and characterization of LAPTM4B, a novel gene upregulated in hepatocellular carcinoma

Oncogene volume 22, pages 5060–5069 (2003)Cite this article

Abstract

Lysosomal-associated protein transmembrane-4 beta (LAPTM4B), a novel gene upregulated in hepatocellular carcinoma (HCC), was cloned using fluorescence differential display, RACE, and RT–PCR. It contains seven exons and encodes a 35-kDa protein with four putative transmembrane regions. Both the N- and C-termini of the protein are proline-rich, and may serve as potential ligands for the SH3 domain. Immunohistochemical analysis localized the protein predominantly to intracellular membranes. Northern blot showed that the LAPTM4B mRNAs were remarkably upregulated in HCC (87.3%) and correlated inversely with differentiation status. LAPTM4B was also overexpressed in many HCC-derived cell lines. It was also highly expressed in fetal livers and certain adult normal tissues including the heart, skeletal muscle, testis, and ovary. Promoter function assays showed a distinct difference in the gene's activities between BEL7402 and HLE cell lines, suggesting that the transcription factors responsible for regulation of the gene in the two cell lines are different, and that possible negative regulatory cis-elements may exist upstream of the promoter region. It was demonstrated that the N-terminus of LAPTM4B was essential for survival of the cells. Cells harboring the full-length LAPTM4B cDNA expression clone displayed a slightly increased efficiency in colony formation. These results suggest that LAPTM4B is a potential protooncogene, whose overexpression is involved in carcinogenesis and progression of HCC. In normal cells, it may also play important roles such as regulation of cell proliferation and survival.

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Acknowledgements

This work was supported by grants from 985 Foundation of Peking University and the National Natural Science Foundation of China (39800076).

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Authors and Affiliations

  1. Department of Cell Biology & Genetics, School of Basic Medical Sciences, Peking University, Beijing, 100083, China

    Gen-Ze Shao, Rou-Li Zhou, Qing-Yun Zhang, Ye Zhang & Jun-Jian Liu

  2. Department of Basic Surgery, Peking Union Medical College Hospital, Beijing, 100032, China

    Jing-An Rui, Xue Wei & Da-Xiong Ye

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  1. Gen-Ze Shao
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Correspondence to Rou-Li Zhou.

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Shao, GZ., Zhou, RL., Zhang, QY. et al. Molecular cloning and characterization of LAPTM4B, a novel gene upregulated in hepatocellular carcinoma. Oncogene 22, 5060–5069 (2003). https://doi.org/10.1038/sj.onc.1206832

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