Identification And Characteristics Of A Novel Liver-Specific Gene

A liver-specific gene was currently identified which encodes a novel zona pellucida (ZP) domain containing protein, named LZP (for liver-specific ZP domain containing protein). The full-length cDNA of human LZP has 2255bp with a complete open reading frame (ORF) of 1635bp coding for 545 amino acids. The gene is localized on chromosome 10q21.3, and spans 40 Kb with 9 encoding exons and 8 introns. Mouse LZP gene localizes on 10B4, consisting of 9 exons, while rat LZP gene localizes on 20ql3, consisting of 10 exons. At the level of mRNA, mouse LZP has two transcripts, while human LZP has only one. We don't know how many transcripts rat LZP has yet. The nucleotide sequence(s) reported has been submitted to the GenBank/EMBL Data Bank with accession number(s) AY013707 (human LZP), AF356506 (mouse LZP variant I), AY180915 (mouse LZP variant II), and AY353853 (rat LZP).Human, mouse and rat LZP protein are highly conserved. They are nearly identical along the whole length, sharing >93% homology. Sequence analysis revealed that LZP consists of mutiple domains, including an N-terminal signal peptide followed by three epidermal growth factor (EGF)-like domains and a ZP domain in C-terminal section.Northern blot revealed that LZP gene is a liver specific gene, which was detected only in liver out of all the tissues examined (23 tissues of human, 8 tissues of mouse). Furthermore, in situ hybridization revealed LZP gene was expressed specifically in hepatocytes. Interestingly, mouse LZP 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 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 stabletransfection didn't inhibit the growth of the cells, implying 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 pathological diagnosis.