MFSD2A is a novel lung tumor suppressor gene modulating cell cycle and matrix attachment

Molecular Cancer

Research

Francesca Colombo¹  Tommaso A. Dragani¹  Felicia S. Falvella¹  Monica Spinola²  Paola Spessotto³  John D. Minna⁴  David S. Shames⁴  Luc Girard⁴  James P. Sullivan⁴ 

[1] Department of Predictive and for Prevention Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy;Department of Predictive and for Prevention Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy;Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, USA;Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA;Divisione di Oncologia Sperimentale 2, Centro di Riferimento Oncologico di Aviano, Aviano, Italy;Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, USA;Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA;

关键词: Normal Lung Tissue;    NSCLC Cell Line;    Linkage Disequilibrium Block;    Normal Human Bronchial Epithelial Cell;    Lung ADCA;   

DOI  :  10.1186/1476-4598-9-62

 received in 2009-10-01, accepted in 2010-03-17,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundMFSD2A (major facilitator superfamily domain containing 2) gene maps on chromosome 1p34 within a linkage disequilibrium block containing genetic elements associated with progression of lung cancer.ResultsHere we show that MFSD2A expression is strongly downregulated in non-small cell lung cancer cell lines of different histotypes and in primary lung adenocarcinomas. Experimental modulation of MFSD2A in lung cancer cells is associated with alteration of mRNA levels of genes involved in cell cycle control and interaction with the extracellular matrix. Exogenous expression of MFSD2A in lung cancer cells induced a G1 block, impaired adhesion and migration in vitro, and significantly reduced tumor colony number in vitro (4- to 27-fold, P < 0.0001) and tumor volume in vivo (~3-fold, P < 0.0001). siRNA knockdown studies in normal human bronchial epithelial cells confirmed the role of MFSD2A in G1 regulation.ConclusionTogether these data suggest that MFSD2A is a novel lung cancer tumor suppressor gene that regulates cell cycle progression and matrix attachment.

【 授权许可】

Unknown   
© Spinola et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.