This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Yendamuri, S. Articles by Calin, G. A. Search for Related Content PubMed PubMed Citation Articles by Yendamuri, S. Articles by Calin, G. A.

Tumor Suppressor Functions of ARLTS1 in Lung Cancers

¹ Kimmel Cancer Center, Thomas Jefferson University; ² Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania; ³ Department of Experimental and Clinical Medicine, Medical School of Catanzaro, "Magna Graecia" University of Catanzaro, Catanzaro, Italy; and ⁴ Department of Experimental and Diagnostic Medicine, Interdepartment Center for Cancer Research, University of Ferrara, Ferrara, Italy

Requests for reprints: George A. Calin, University of Texas, M. D. Anderson Cancer Center, Experimental Therapeutics Department, Houston, TX 77030. Phone: 713-792-5461; Fax: 713-745-4528/1710; E-mail: gcalin{at}mdanderson.org.

ARLTS1 is a newly characterized tumor suppressor gene located at chromosome 13q14.3 and involved in the pathogenesis of various types of tumors: two single-nucleotide polymorphisms, one of them responsible for protein truncation, were found statistically associated with familial malignancies, whereas DNA hypermethylation and genomic deletions have been identified as a mechanism of ARLTS1 down-regulation in sporadic cancers. We found that in a large portion of lung carcinomas (37%) and in all analyzed lung cancer cell lines, ARLTS1 is strongly down-regulated due to DNA methylation in its promoter region. After its restoration by adenoviral transduction, ARLTS1-negative A549 and H1299 cells underwent apoptosis and inhibition of cell growth. Furthermore, ARLTS1 reexpression significantly reduced the ability of A549 and H1299 to form tumors in nude mice. Finally, we identified 650 transcripts differentially expressed after restoration of ARLTS1 expression in A549 cells, suggesting that various pathways involved in cell survival, proliferation, signaling, and development mediate the effects of wild-type ARLTS1 in a lung cancer system. [Cancer Res 2007;67(16):7738–45]