Biological function of a novel gene overexpressed in human hepatocellular carcinoma

Objective To clone the full-length of a differentially expressed cDNA fragm ent, LC27, and study its biological function tentatively. Methods Northern blot was used to analyze the expression pattern of LC27 in hepatocellular carcinoma, matched nontumor liver tissues, fetal liver and normal adult liver tissues, as well as BEL-7402 hepatocellular carcinoma ce ll line ESTs splicing and 5' rapid amplification of cDNA ends (5' RACE) wer e used to clone the full-length of LC27 cDNA. An antisense oligodeoxynucleo tide approach was used to investigate the biological role of the gene in th e proliferation of BEL-7402 cells. Results A 2186 bp novel cDNA with an open reading frame encoding a 283 amin o acid protein was cloned. Analysis of the deduced amino acid sequence indi cated that it is 38% (88/229) identical to human Golgi 4-transmembrane span ning transporter MTP. The gene and the encoded protein was termed hepatocel lular carcinoma overexpressed transmembrane protein (hotp) and HOTP, respec tively. Hotp mRNA was almost undetectable in normal adult liver and fetal l iver tissues. However, it was significantly up-regulated in hepatocellular carcinoma and some matched nontumor liver tissues, as well as BEL-7402 cell s. The proliferation of BEL-7402 cells was suppressed by an antisense oligo deoxynucleotide against hotp mRNA at a concentration of 50 mu g/ml. Conclusion HOTP may be an integral membrane transporter protein. The overex pression of the gene in hepatocellular carcinoma may play an important role in hepatocarcinogenesis and disease progression.