Molecular cloning and characterization of a novel gene which is highly expressed in hepatocellular carcinoma.
To gain new insight into the molecular mechanism underlying the pathogenesis of human primary hepatocellular carcinoma (HCC), we searched for HCC-specific molecules through screening genes that are differentially expressed between cancerous and noncancerous counterparts of liver and identified a novel HCC-associated gene, HCCA1 encoding a approximately 80 kDa cytoplasmic protein that contains several proline-rich motifs likely for SH3-binding. HCCA1 transcript, albeit present in some adult tissues, is up-regulated selectively in HCC but not in other tumor cells. High expression of HCCA1 occurs as a late event frequently (89.2%) in HCCs and correlated significantly with the degree of tumor progression. When treated with antisense oligonucleotides to HCCA1, HCCA1 expression in HCC cells (HuH-7) was effectively suppressed and cell growth was down-regulated in a time- and dose-dependent manner. Furthermore, HuH-7 cells harboring the HCCA1 antisense expression clone displayed a remarkably reduced efficiency in colony formation. Together, these data strongly suggest that HCCA1 is a positive effector in cell proliferation and contributes to HCC carcinogenesis and progression. We believe that this protein will serve as a novel useful marker for HCC and is a potential target for pharmaceutical intervention of this malignant disease.
International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgical Institute, Secondary Military Medical University, Shanghai 200438, PR China.
Jin-Zhang
JZ
Zeng
Hong-Yang
HY
Wang
Zheng-Jun
ZJ
Chen
Axel
A
Ullrich
Meng-Chao
MC
Wu
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000235:genetics; D003001:Cloning, Molecular; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D014157:Transcription Factors; D015854:Up-Regulation
D018797:Cell Cycle Proteins; D016376:Oligonucleotides, Antisense; D011506:Proteins; D014157:Transcription Factors; C456659:YY1AP1 protein, human