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Two variants of the human hepatocellular carcinoma‐associated HCAP1 gene and their effect on the growth of the human liver cancer cell line Hep3B
Author(s) -
Wan Dafang,
He Mei,
Wang Junru,
Qiu Xiaokun,
Zhou Wei,
Luo Zewei,
Chen Jianguo,
Gu Jianren
Publication year - 2004
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.10293
Subject(s) - biology , single nucleotide polymorphism , haplotype , gene , snp , genetics , microbiology and biotechnology , allele , cell growth , ectopic expression , minor allele frequency , genotype
We have cloned a cDNA from chromosome band 17p13.3, designated as HCAP1 (HCC‐associated protein 1, originally named HC56 ). Database searches revealed that HCAP1 shares most of its open reading frame with GEMIN4 . Single nucleotide polymorphism (SNP) screening revealed a high incidence of SNP in the coding region of HCAP1 (12 SNP sites). A collection of 140 controls and 22 cases from the Qidong area was genotyped at 6 SNP sites. The 22 cases exhibited higher frequencies of minor alleles than did the controls, and 2 sites revealed significant differences between the controls and the cases. We constructed 2 haplotypes, HCAP1‐N (with common alleles at 5 SNP sites) and HCAP1‐M (with minor alleles at 5 SNP sites), in a mammalian expression system. Both haplotypes resulted in a remarkable reduction in colony formation and suppression of cell growth after being transfected into the human hepatocellular carcinoma (HCC) cell line. The inhibitory effect of HCAP1‐N was stronger than that of HCAP1‐M . Different haplotypes also resulted in different gene expression profiles in the Hep3B cell line according to an examination of 588 genes on an Atlas membrane. The expression induced by HCAP1‐M caused an up‐regulation of genes involved in cellular proliferation and a down‐regulation of genes involved in cellular apoptosis and DNA repair. These results, in addition to the statistical data, are biological evidence that the HCAP1‐M variant of HCAP1 has a reduced inhibitory effect on hepatocarcinoma cell growth and an impaired DNA repair system. This suggests that HCAP1‐M may be related to cancer susceptibility. © 2003 Wiley‐Liss, Inc.