LFIRE-1/HFREP-1, a liver-specific gene, is frequently downregulated and has growth suppressor activity in hepatocellular carcinoma

	LFIRE-1/HFREP-1, a liver-specific gene, is frequently downregulated and has growth suppressor activity in hepatocellular carcinoma
	Yan, J; Yu, YL; Wang, N; Chang, YC; Ying, H; Liu, WZ; He, J; Li, SQ; Jiang, WL; Li, YL
刊名	ONCOGENE
	2004
卷号	23 期号:10 页码:1939-1949
关键词	hepatocellular carcinoma (HCC) 8p22 fibrinogen-related domain liver-specific expression differentiation
通讯作者	Xu, YH (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Lab Mol & Cellular Oncol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,yhxu@sunm.shcnc.ac.cn
英文摘要	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 50 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.
学科主题	Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity
类目[WOS]	Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
关键词[WOS]	CANCER EPIGENETICS ; CHROMOSOME 8P ; CLONING ; PROGRESSION ; STAGE ; ARM
收录类别	SCI
语种	英语
WOS记录号	WOS:000220129500016
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/2151]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Yan, J,Yu, YL,Wang, N,et al. LFIRE-1/HFREP-1, a liver-specific gene, is frequently downregulated and has growth suppressor activity in hepatocellular carcinoma[J]. ONCOGENE,2004,23(10):1939-1949.
APA	Yan, J.,Yu, YL.,Wang, N.,Chang, YC.,Ying, H.,...&Xu, YH.(2004).LFIRE-1/HFREP-1, a liver-specific gene, is frequently downregulated and has growth suppressor activity in hepatocellular carcinoma.ONCOGENE,23(10),1939-1949.
MLA	Yan, J,et al."LFIRE-1/HFREP-1, a liver-specific gene, is frequently downregulated and has growth suppressor activity in hepatocellular carcinoma".ONCOGENE 23.10(2004):1939-1949.