Isolation and characterization of a novel oncogene, amplified in liver cancer 1, within a commonly amplified region at 1q21 in hepatocellular carcinoma.
Amplification of 1q21 is the most frequent genetic alteration in human hepatocellular carcinoma (HCC), being detected in 58%-78% of primary HCC cases by comparative genomic hybridization. Recently, we isolated a candidate oncogene, Amplified in Liver Cancer 1 (ALC1), from 1q21 by hybrid selection. Here we demonstrate that ALC1 was frequently amplified and overexpressed in HCC. ALC1-transfected cells possessed a strong oncogenic ability, increasing the colony formation in soft agar and increasing the tumorigenicity in nude mice, which could be effectively suppressed by small interfering RNA against ALC1. Functional studies showed that overexpression of ALC1 could promote G1/S phase transition and inhibit apoptosis. Molecular studies revealed that the oncogenic function of ALC1 might be associated with its roles in promoting cell proliferation by down-regulating p53 expression.


CONCLUSIONS
These results suggest that ALC1 is the target oncogene within the 1q21 amplicon and plays a pivotal role in HCC pathogenesis.
Ma
Ning-Fang
NF
Department of Histology and Embryology, Guangzhou Medical College, Guangzhou, China.
Hu
Liang
L
Fung
Jackie M
JM
Xie
Dan
D
Zheng
Bo-Jian
BJ
Chen
Leilei
L
Tang
Dong-Jiang
DJ
Fu
Li
L
Wu
Zhenguo
Z
Chen
Muhan
M
Fang
Yan
Y
Guan
Xin-Yuan
XY
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002878:Chromosomes, Human, Pair 1; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D015513:Oncogene Proteins / Q000235:genetics*; D009857:Oncogenes
D015513:Oncogene Proteins