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A Functional Role for KLF6-SV1 in Lung Adenocarcinoma Prognosis and Chemotherapy Response

Departments of ¹ Genetics and Genomic Sciences, ² Oncological Sciences, and ³ Medicine, the Mount Sinai School of Medicine, New York, New York; and ⁴ Department of Surgery, University of Michigan, Ann Arbor, Michigan

Requests for reprints: Goutham Narla, Mount Sinai School of Medicine, 1425 Madison Avenue, Room 14-22, New York, NY 10029. Phone: 212-659-9218; E-mail: Goutham.Narla@mssm.edu.

Key Words: oncogene • lung cancer • Krupppel like • KLF6 • chemotherapy

Kruppel-like factor 6 (KLF6) is a tumor suppressor gene that is functionally inactivated in human cancer by loss of heterozygosity, somatic mutation, decreased expression, and increased alternative splicing into an oncogenic splice variant, KLF6-SV1. Here we show that increased expression of KLF6-SV1 is associated with decreased survival in patients with lung adenocarcinoma. In addition, KLF6-SV1 is a novel antiapoptotic protein in lung cancer cell lines, and targeted reduction of KLF6-SV1 using siRNA induces apoptosis both alone and in combination with the chemotherapeutic drug cisplatin. Together, these findings highlight a critical role for KLF6-SV1 in lung cancer, and show a potential novel therapeutic strategy for the treatment of lung cancer. [Cancer Res 2008;68(4):965–70]

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