Identification of a human hepatocellular carcinoma-associated tumor suppressor gene by differential display polymerase chain reaction.
Differential gene expression between the normal human liver and a cell line derived from human hepatocellular carcinoma (HCC) was studied using the differential display polymerase chain reaction technique. One gene (mitochondria proteolipid like gene, MPL), whose expression was found to be repressed in the HCC cell line compared to normal liver, was cloned and sequenced. Amino acid sequence translated from the nucleotide sequence had a 73% homology with the carboxyl terminus of a mitochondria proteolipid (MPLP) isolated from beef heart. Northern blot analysis showed that the expression of the 3 kb MPL transcript was undetectable in 20 of 45 (44%) of human hepatocellular carcinomas, whereas only 1 of 14 (17%) of cirrhotic livers without HCC had undetectable expression when compared to normal livers. Hence MPL may be a candidate tumor suppressor gene for human HCC. This decrease in MPL expression was not due to gross alteration of its genomic DNA.
Wu
G S
GS
Pittsburgh Transplantation Institute, University of Pittsburgh School of Medicine, PA 15213, USA.
Kar
S
S
Carr
B I
BI
D000595:Amino Acid Sequence; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008099:Liver / Q000502:physiology; D008103:Liver Cirrhosis / Q000503:physiopathology; D008113:Liver Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D011510:Proteolipids / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D025521:Tumor Suppressor Proteins
D009363:Neoplasm Proteins; D011510:Proteolipids; D025521:Tumor Suppressor Proteins; C095379:mitochondria proteolipid-like protein, human