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RBMY, a male germ cell-specific RNA-binding protein, activated in human liver cancers and transforms rodent fibroblasts

Oncogene volume 23, pages 5815–5822 (2004)Cite this article

Abstract

The RNA-binding motif (RRM) gene on Y chromosome (RBMY), encoding a male germ cell-specific RNA-binding protein associated with spermatogenesis, was found inserted by hepatitis B virus (HBV) DNA in one childhood hepatocellular carcinoma (HCC). This study is aimed to explore the oncogenic potential of the RBMY protein. The RBMY transcripts, expressed exclusively in the testis of normal people, were detected by reverse transcription–polymerase chain reaction in 36% of HCCs from 90 males and in 67% of hepatoblastoma from six boys. The nontumor liver counter parts, cirrhotic liver tissues from children with biliary atresia, and other types of cancers, such as bile duct, colon, stomach, lung, prostate, and kidney, were all negative for RBMY expression. One to four types of RBMY transcripts, including wild type and variants with N-terminal RRM deletion, C-terminal SRGY (serine-arginine-glycine-tyrosine) boxes deletion, or deletion of both domains, were found in the testis and liver cancer tissues. The wild-type RBMY protein was expressed in the nucleus and demonstrated its tumorigenicity by transformation of mouse fibroblast NIH3T3 cells and in vivo tumor formation. The RBMY variant protein with deletion of C-terminal exons 9–12 was trapped in the cytoplasm and showed decreased tumorigenicity. Our results suggest that RBMY is a new candidate oncogene specific for male liver cancer.

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Acknowledgements

We thank Dr Lih-Hwa Hwang of the Hepatitis Research Center, National Taiwan University Hospital for reading the manuscript and helpful suggestion, and Dr Li-Min Huang of the Department of Pediatrics, National Taiwan University Hospital for giving the plasmid pcDNA3-3HA. This work was supported by Grants NHRI-EX91-9117BN and NHRI-EX92-9117BN from the National Health Research Institute (to MHC) and NHRI-GT-EX89B701L (to HCH).

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Authors and Affiliations

  1. Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taiwan

    Daw-Jen Tsuei, Wei-Chun Chou, Chung-Jung Chang, Yen-Hsuan Ni & Mei-Hwei Chang

  2. Department of Pathology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taiwan

    Hey-Chi Hsu & Yung-Ming Jeng

  3. Department of Surgery, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taiwan

    Po-Huang Lee, Chiung-Nien Chen & Yung-Chie Lee

  4. Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taiwan

    Yeong-Shiau Pu

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Correspondence to Mei-Hwei Chang.

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Tsuei, DJ., Hsu, HC., Lee, PH. et al. RBMY, a male germ cell-specific RNA-binding protein, activated in human liver cancers and transforms rodent fibroblasts. Oncogene 23, 5815–5822 (2004). https://doi.org/10.1038/sj.onc.1207773

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