title: Upregulation of LAPTM4B-35 promotes malignant transformation and tumorigenesis in L02 human liver cell line.
abstract: Hepatocellular carcinoma (HCC) is one of the most frequent malignant neoplasms worldwide and is the second leading cause of cancer death in China. We have previously demonstrated that LAPTM4B-35, encoded by lysosomal protein transmembrane 4 beta gene, is overexpressed in over 80% of HCCs and is a novel-independent prognostic factor for metastasis, recurrence, and postoperative survival in HCC. In this study, we investigated the role of LAPTM4B-35 in malignant transformation and tumorigenesis using L02 cells, a cell line originated from human normal liver cells. Our data show that replication-deficient adenovirus vector-mediated upregulation of LAPTM4B-35 promotes anchorage-independent proliferation and resistance to adriamycin-induced apoptosis. Study of the underlying mechanisms demonstrated alterations of molecular events involved in these processes, which included the activation of phosphoinositide 3-kinases (PI3K)/serine/threonine protein kinase B (PKB/AKT)/bcl-xL/bcl-2-associated death promoter homolog (Bad) signaling pathway, inhibition of caspase-3 activation, upregulation of Bcl-2, and downregulation of Bax. In addition, upregulation of LAPTM4B-35 in L02 cells resulted in tumorigenesis in 100% (6/6) of inoculated nude mice and accelerated the death of mice with xenografts in vivo. In conclusion, LAPTM4B-35 promotes malignant transformation and tumorigenesis in human liver L02 cell line through promotion of deregulated proliferation and inhibition of apoptosis. These findings suggest that overexpression of LAPTM4B-35 may play a critical role in hepatocarcinogenesis and therefore, may be a therapeutic target for HCC.
authors: Department of Cell Biology, Health Science Center, Peking University, Beijing, China.
authors: Li
authors: L
authors: Li
authors: Yi
authors: Y
authors: Shan
authors: Hua
authors: H
authors: Yang
authors: Sha
authors: S
authors: Zhang
authors: Ming
authors: M
authors: Lin
authors: Ping
authors: P
authors: Zhu
authors: Xin-Yu
authors: XY
authors: Chen
authors: Jing
authors: J
authors: Yi
authors: Michael A
authors: MA
authors: McNutt
authors: Gen-Ze
authors: GZ
authors: Shao
authors: Rou-Li
authors: RL
authors: Zhou