EBV Conference 2008 Guangzhou - Baylor College of Medicine

127 (RegID: 1174; 1175)
Xiangning Zhang
Institution: Guangdong Medical College
e-mail: zhangxn_2006@126.com
TUMOR SUPPRESSOR DELETED IN LIVER CANCER-1 (DLC-1) GENE TRIGGERS
APOPTOSIS IN NPC CELLS BY PERTURBING MITOCHONRIA (MI)
Xiangning Zhang1*, Chun-Ming Wong2, Peichun Huang1 and Wenlin Huang3
1Department of Pathophysiology, Guangdong Medical College, Zhanjiang Guangdong524023, China;
2Department of Pathology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam,
Hong Kong, China; 3State Key Laboratory of Oncology in South China, Sun Yat Sen University Cancer
Center, Guangzhou, Guangdong 510060, China. (*E-mail: zhangxn_2006@126.com)
Posterabstract:
DLC-1 is a bona fide tumor suppressor gene (TSG) mapped to chromosome 8p22-p21, a region frequently
deleted in human malignancies. DLC-1 gene encodes a GTPase activating protein (GAP), which
negatively regulates the activity of Ras homolog (Rho) family. RhoGAP activity of DLC-1 plays an
important role in regulating cell motility and suppressing cancer metastasis. Genetic and epigenetic
inactivation of DLC1 is frequently found in human cancers, including nasopharyngeal carcinoma (NPC)
and hepatocellular carcinoma (HCC), two major endemic tumors in southern China. The anti-proliferative
effect of DLC-1 is evidenced with its inhibition of colony formation in NPC cells. The pro-apoptotic
function of DLC-1 has also been suggested, but the underlying mechanisms remain unanswered. Since the
human DLC-1 ortholog, DLC-2 was found to be localized on MI membrane; DLC-1 has been
hypothesized to play a role in MI dependent apoptosis. To test this hypothesis, NPC cells were transfected
with EGFP-tagged DLC-1 plasmid, and stained with tetramethylrhodamine ethyl ester (TMRE).
Microscopically, DLC-1 signal was found to localize in cytoplasm and was significantly overlapped with
TMRE signal. In addition, ectopic expression of DLC-1 dropped MI membrane potential (MMP) as
evidenced by flow cytometry-based TMRE staining. Furthermore, we demonstrated that blocking of death
receptor pathway(DR) by dominant negative FADD failed to suppress DLC-1 mediated MMP changes,
suggesting that DLC-1 induced apoptosis was independent to DR pathway. We will next evaluate the
effect of blocking stress-induced pathway with specific inhibitors on DLC-1 induced apoptosis. In
summary, our results suggest that DLC-1 protein may target to MI membrane and induce apoptosis. The
re-expression of DLC-1 is of mild pro-apoptotic activity; and thus it prompted us to test whether DLC-1
would potentiate apoptosis induced by the challenge of genotoxins and death ligands, and our study may
provide insights to design of novel therapeutic modality for cancers.
EBV Conference 2008 Guangzhou
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