A specific splicing variant of SVH, a novel human armadillo repeat protein, is up-regulated in hepatocellular carcinomas.
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with poor prognosis. By representational difference analysis (RDA), a novel human gene designated SVH, up-regulated in the clinical HCC sample, was identified. The deduced SVH protein consisted of 343 amino acids with a transmembrane domain and an armadillo repeat. Northern blot revealed that SVH was expressed in most human adult tissues. Four variants of SVH, SVH-A, -B, -C, and -D, resulting from alternative splicing in the coding region of the SVH transcript, were observed and were all localized in endoplasmic reticulum (ER). Up-regulation of SVH-B, but not the other variants, was evident in about 60% (28 of 46) of HCC samples, detected by quantitative real-time PCR. Human liver cell line QSG-7701, transfected with SVH-B, acquired an accelerated growth rate and tumorigenicity in nude mice, whereas inhibition of SVH-B in hepatoma cell line BEL-7404, using antisense oligodeoxynucleotides, induced apoptosis. It is suggested that the splicing variants of SVH have distinct biological functions, and SVH-B may play an important role in hepatocarcinogenesis.
Huang
Ruimin
R
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, the Chinese Academy of Sciences, 200031 Shanghai, China.
Xing
Zhigang
Z
Luan
Zhidong
Z
Wu
Tangming
T
Wu
Xin
X
Hu
Gengxi
G
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000601:surgery; D002455:Cell Division; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000601:surgery; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D010957:Plasmids; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics*; D014162:Transfection
C476102:ARMC10 protein, human; D017931:DNA Primers; D018076:DNA, Complementary; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D015534:Trans-Activators