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- Title
LFIRE-1/HFREP-1, a liver-specific gene, is frequently downregulated and has growth suppressor activity in hepatocellular carcinoma.
- Authors
Jun Yan; Yanlin Yu, David K.; Nan Wang; Yunchao Chang, David K.; Hao Ying; Weizhong Liu, David K.; Jin He; Shenqing Li, David K.; Wanli Jiang; Yuli Li, David K.; Huimin Liu; Hongyang Wang, David K.; Yonghua Xu, David K.
- Abstract
We have previously identified several novel genes, which are differentially expressed among human normal liver and hepatocellular carcinomas (HCCs). The full-length liver fibrinogen-related gene-1 (LFIRE-1) cDNA was cloned from the human normal liver cDNA library. LFIRE-1 is highly homologous to HFREP-1 with discrepancy at 5' untranslated region (UTR) and encodes the same fibrinogen-related protein, which suggest that these two sequences might be alternative splicing forms of the same gene, LFIRE-1/HFREP-1, located at human chromosome 8p22. The LFIRE-1 and HFREP-1 are specifically expressed in normal human liver tissue, but reduced or undetectable in most of HCC specimens at both RNA and protein level. Furthermore, the reduction or nonexpression of LFIRE-1/HFREP-1 is significantly associated with the degree of tumor differentiation. Loss of heterozygosity (LOH) analysis revealed allelic loss of LFIRE-1/HFREP-1 on chromosome 8p22 in 57.1% (24/42) of HCC specimens. We detected three inactivation mutations among 45 cases of HCC specimens examined, two of which lost the remaining allele and the third had a replacement of conserved cysteine residue with glycine residue. Notably, the downregulation of LFIRE-1/HFREP-1 expression is frequently associated with allelic loss. The reduction of LFIRE-1/HFREP-1 expression by antisense approach enhances cancer cell proliferation and colony formation in soft agar. Moreover, restoration of exogenous wild-type LFIRE-1/HFREP-1 expression but not LFIRE-1/HFREP-1 missense mutations in human HCC cells inhibited their anchorage-dependent or -independent growth in vitro, and suppressed their tumorigenicity in nude mice. In conclusion, our data demonstrated that liver-specific gene LFIRE-1/HFREP-1 was frequently downregulated and might possess growth suppressor activity in HCC.Oncogene (2004) 23, 1939-1949. doi:10.1038/sj.onc.1207306 Published online 23 February 2004
- Subjects
LIVER cancer; FIBRINOGEN; TUMOR suppressor proteins; GENETIC mutation; CANCER cell proliferation
- Publication
Oncogene, 2004, Vol 23, Issue 10, p1939
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1207306