జర్నల్ ఆఫ్ క్లినికల్ & ఎక్స్‌పెరిమెంటల్ పాథాలజీ

నైరూప్య

Overexpression of the Novel Tumor Suppressor Gene FUS1 Suppresses the Growth of Small Cell Lung Cancer Cells

Roza Zandi, Kai Xu, Hans S. Poulsen, Jack A. Roth and Lin Ji

FUS1, also known as tumor suppressor candidate 2 (TUSC2), is a novel candidate tumor suppressor gene (TSG) frequently inactivated in human lung cancer. Loss of FUS1 protein expression is found in almost all small cell lung cancer (SCLC) cell lines and tumor specimens. Therefore, restoration of normal FUS1 function by gene transfer could serve as a potential therapeutic strategy for the treatment of SCLC. Here we investigated the effect of exogenous expression of FUS1 by plasmid-mediated gene transfer on tumor cell growth and apoptosis induction in FUS1-defective SCLC cells. Transfection of SCLC cells with wild-type FUS1 (wt-FUS1) showed in vitro growth inhibition and a marked suppression of colony formation compared to cells transfected with an empty vector (EV) or a myristoylation-defect mutant FUS1 (mt-FUS1). Forced expression of wt-FUS1 also increased the apoptotic cell population at Sub-G0/G1 in SCLC cells compared to EV- and mt-FUS1-transfected controls, which was associated with a decreased level of pro-caspase-3 and an increased level of PARP cleavage. Our results demonstrate the potential tumor suppression function of FUS1 in SCLC cells and suggest that FUS1-mediated gene therapy could be a useful therapeutic strategy for the treatment of SCLC.