Two variants of the human hepatocellular carcinoma-associated HCAP1 gene and their effect on the growth of the human liver cancer cell line Hep3B.
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.
Wan
Dafang
D
National Laboratory for Oncogenes and Related Genes, Cancer Institute of Shanghai Jiao Tong University, People's Republic of China.
He
Mei
M
Wang
Junru
J
Qiu
Xiaokun
X
Zhou
Wei
W
Luo
Zewei
Z
Chen
Jianguo
J
Gu
Jianren
J
D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D002681:China; D015536:Down-Regulation / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008113:Liver Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D010455:Peptides; D020641:Polymorphism, Single Nucleotide; D015854:Up-Regulation / Q000235:genetics
D009363:Neoplasm Proteins; D010455:Peptides; C442243:dermcidin