, Volume 130, Issue 12, pp 719-727
Date: 31 Aug 2004

KIAA0008 gene is associated with invasive phenotype of human hepatocellular carcinoma—a functional analysis

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

Purpose

To investigate the function of the KIAA0008 gene, one of the leading genes in the signature associated with hepatocellular carcinoma (HCC) metastasis selected by cDNA microarray, and especially its possible roles in invasion and metastasis of hepatocellular carcinoma.

Methods

Expression levels of KIAA0008 in 27 primary tumors and 23 matched non-tumor liver tissues from HCC patients, and four HCC cell lines with different metastatic potentials were detected by semi-quantitative RT-PCR and real-time RT-PCR. Recombinant expression plasmid vectors of the KIAA0008 gene were constructed and transfected into HCC cells. The subcellular localization of the KIAA0008 gene product and in vitro effects of KIAA0008 overexpression on proliferation and invasion of HCC cell line were also investigated.

Results

Expression levels of KIAA0008 in HCC tissues were statistically higher than those of paired non-tumorous liver tissues (P<0.001, paired Wilcoxon test), and in HCCs with high invasiveness these were statistically higher than those with low invasiveness (P=0.002, Mann-Whitney test). In the four HCC cell lines with an identical genetic background and stepwise higher invasiveness potentials, its expression was consistent with their invasiveness potential. The KIAA0008 gene product was concentrated on the nucleus and cell membrane of HCC cells, without any distribution in the cytoplasm. Overexpression of KIAA0008 in the MHCC97L cell line resulted in increased cell proliferation, colony formation, and invasion.

Conclusions

KIAA0008 expression is associated with invasiveness of HCC; overexpression of KIAA0008 leads to a more invasive phenotype of HCC cell lines.

This work was supported in part by the National Foundation for the Excellent Younger Researcher of China (30325041), the “863” R & D High-tech Key Project (2002BA711A02–4), the “973” State Key Basic Research Program Grant of China (G1998051211), the Fund for the Innovative Research Group in Shanghai, and the Fund for Outstanding Scholars of the New Era of the Ministry of Education in China (2003)