Biological Function of a Novel Gene Overexpressed in Human Hepatocellular Carcinoma

Objective: To clone the full-length of a differentially expressed cDNA fragment, 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 cell line ESTs splicing and 5' rapid amplification of cDNA ends (5' RACE) were used to clone the full-length of LC27 cDNA. An antisense oligodeoxynucleotide approach was used to investigate the biological role of the gene in the proliferation of BEL-7402 cells.

Results: A 2186 bp novel cDNA with an open reading frame encoding a 283 amino acid protein was cloned. Analysis of the deduced amino acid sequence indicated that it is 38% (88/229) identical to human Golgi 4-transmembrane spanning transporter MTP. The gene and the encoded protein was termed hepatocellular carcinoma overexpressed transmembrane protein (hotp) and HOTP, respectively. Hotp mRNA was almost undetectable in normal adult liver and fetal liver tissues. However, it was significantly up-regulated in hepatocellular carcinoma and some matched nontumor liver tissues, as well as BEL-7402 cells. The proliferation of BEL-7402 cells was suppressed by an antisense oligodeoxynucleotide against hotp mRNA at a concentration of 50 micrograms/ml.

Conclusion: HOTP may be an integral membrane transporter protein. The overexpression of the gene in hepatocellular carcinoma may play an important role in hepatocarcinogenesis and disease progression.