Increased expression of glycosyl-phosphatidylinositol anchor attachment protein 1 (GPAA1) is associated with gene amplification in hepatocellular carcinoma.
Glycosyl-phosphatidylinositol (GPI) anchor attachment protein 1 (GPAA1) transcript level was frequently up-regulated in our earlier study on gene expression profile. We therefore analyzed the potential involvement of GPAA1 in hepatocellular carcinoma (HCC) as GPAA1 gene locates at chromosome 8q24.3 which chromosome region is frequently amplified in HCCs. In this study, we observed that GPAA1 transcript in the HCCs (n = 93) showed a significantly higher expression level compared with their paralleled adjacent nontumor liver tissues, cirrhosis (n = 15) and normal (n = 16) liver tissues using real-time quantitative RT-PCR (p < 0.005). We also demonstrated that GPAA1 protein up-regulation was common in HCCs (90%, 9/10), and GPAA1 gene was frequently amplified (73%, 11/15) using quantitative microsatellite analysis. Increased GPAA1 expression was significantly associated with HCCs poor cellular differentiation (p = 0.011) and poor prognosis (p = 0.010). We then modulated the GPAA1 expression level in HCC cells (Hep3B) by transfection experiments, which was shown to positively regulate cell adhesion ability (p = 0.004) and proliferation rate (p = 0.037). Our data revealed GPAA1 gene amplification with overexpression of RNA and protein in HCC. GPAA1 is a potential amplification target of chromosome 8q and responsible to regulate tumor cells behavior.
Ho
Jenny C
JC
Centre for the Study of Liver Disease, The University of Hong Kong, Pokfulam, Hong Kong, China.
Cheung
Siu Tim
ST
Patil
Mohini
M
Chen
Xin
X
Fan
Sheung Tat
ST
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics / Q000821:virology; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
C093316:GPAA1 protein, human; D008562:Membrane Glycoproteins; D012333:RNA, Messenger