A functional role for KLF6-SV1 in lung adenocarcinoma prognosis and chemotherapy response

Cancer Res. 2008 Feb 15;68(4):965-70. doi: 10.1158/0008-5472.CAN-07-2604. Epub 2008 Feb 4.

Abstract

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.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / physiology
  • Cell Growth Processes / physiology
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • DNA Damage
  • Down-Regulation
  • Humans
  • Kruppel-Like Factor 6
  • Kruppel-Like Transcription Factors / biosynthesis*
  • Kruppel-Like Transcription Factors / genetics
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Prognosis
  • Protein Isoforms
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins / genetics
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Transfection

Substances

  • Antineoplastic Agents
  • KLF6 protein, human
  • Kruppel-Like Factor 6
  • Kruppel-Like Transcription Factors
  • Protein Isoforms
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Cisplatin