title: RBMY, a male germ cell-specific RNA-binding protein, activated in human liver cancers and transforms rodent fibroblasts.
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.
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taiwan.
authors.forename: Daw-Jen
authors.initials: DJ
authors.lastname: Tsuei
authors.forename: Hey-Chi
authors.initials: HC
authors.lastname: Hsu
authors.forename: Po-Huang
authors.initials: PH
authors.lastname: Lee
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
authors.forename: Yeong-Shiau
authors.initials: YS
authors.lastname: Pu
authors.forename: Chiung-Nien
authors.initials: CN
authors.lastname: Chen
authors.forename: Yung-Chie
authors.initials: YC
authors.lastname: Lee
authors.forename: Wei-Chun
authors.initials: WC
authors.lastname: Chou
authors.forename: Chung-Jung
authors.initials: CJ
authors.lastname: Chang
authors.forename: Yen-Hsuan
authors.initials: YH
authors.lastname: Ni
authors.forename: Mei-Hwei
authors.initials: MH
authors.lastname: Chang
mesh_terms: D016475:3T3 Cells / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015197:Carcinogenicity Tests; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics; D009687:Nuclear Proteins; D009928:Organ Specificity; D016601:RNA-Binding Proteins / Q000235:genetics*; D012016:Reference Values; D017384:Sequence Deletion; D013737:Testis / Q000502:physiology*
chemical_list: D009687:Nuclear Proteins; C501499:RBMY1A1 protein, human; D016601:RNA-Binding Proteins; C501500:Rbmy protein, mouse