A novel liver-specific zona pellucida domain containing protein that is expressed rarely in hepatocellular carcinoma.
We currently identified a liver-specific gene that encodes a novel zona pellucida (ZP) domain-containing protein named liver-specific ZP domain-containing protein (LZP). The full-length complementary DNA (cDNA) of human LZP has 2,255 bp with a complete open reading frame (ORF) of 1,635 bp. The gene is localized on chromosome 10q21.3 and spans 40 kb with 9 encoding exons and 8 introns. The deduced protein sequence has 545 amino acid residues, with an N-terminal signal peptide followed by 3 epidermal growth factor (EGF)-like domains and a ZP domain in C-terminal section. Interestingly, human LZP is expressed specifically in liver out of 23 tissues examined, and its mouse counterpart was detected at very early stage during embryo development. Moreover, LZP can be secreted into blood, albeit the protein was localized mainly on the nuclear envelop of hepatocytes. Most importantly, LZP is down-regulated in hepatocellular carcinoma (HCC) and HCC cell lines; meanwhile, the decreased level of hLZP messenger RNA (mRNA) could, at least in some HCC samples, be related to the methylation status of the putative LZP promoter. However, overexpression of hLZP in HCC cell line SMMC-7721 and human liver cell line L02 by stable cell transfection did not inhibit cell growth, implying that the down-regulation of hLZP in HCC might be a consequence of the dedifferentiation involved in hepatocarcinogenesis. In conclusion, these data suggest that LZP is a liver-specific protein involved possibly in hepatocellular function and development, and the protein could be used as potential negative biomarker for HCC pathologic diagnosis.
Xu
Zhi-Gang
ZG
Chinese National Human Genome Center at Shanghai, Shanghai, China.
Du
Jian-Jun
JJ
Zhang
Xin
X
Cheng
Zhi-Hong
ZH
Ma
Zhen-Zhong
ZZ
Xiao
Hua-Sheng
HS
Yu
Li
L
Wang
Zhi-Qin
ZQ
Li
Yu-Yang
YY
Huo
Ke-Ke
KK
Han
Ze-Guang
ZG
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D019175:DNA Methylation; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D015044:Zona Pellucida
D018076:DNA, Complementary; D008565:Membrane Proteins; C477697:OIT3 protein, human