title: Krüppel-like factor 4 functions as a tumor suppressor in cervical carcinoma.
abstract: BACKGROUND
  The Krüppel-like factor 4 (KLF4) protein, a zinc finger transcription factor that is highly expressed in epithelial tissues such as the gut and skin, has been implicated in both tumor suppression and progression. However, the role of KLF4 in human cervical carcinoma is still unclear.
  
  
  METHODS
  The expression of KLF4 in cervical carcinoma tissues and cervical cancer cell lines was examined with immunohistochemistry and Western blot assay. The effects of KLF4 silencing and overexpression on the cell proliferation, cell viability, and tumor formation of cervical cancer cells were investigated.
  
  
  RESULTS
  KLF4 protein expression showed a pattern of gradual decrease from normal cervix to cervical carcinoma in situ and then to invasive cervical carcinomas (P < .05). Overexpression of KLF4 in SiHa and C33A cells resulted in significantly inhibited cell growth and significantly attenuated tumor formation. Consistently, KLF4 silencing in HeLa cells significantly promoted cell growth and tumor formation. Furthermore, KLF4 overexpression caused cell cycle arrest at the G1/S transition, along with the up-regulated expression of p27(Kip1) protein. Promoter analysis revealed that KLF4 transactivated the expression of p27(Kip1) through the specific motif that is between the nucleotides of -435 and -60 in its promoter. The results from chromatin immunoprecipitation assays demonstrated the physical interaction between KLF4 protein and this specific motif in p27(Kip1) promoter.
  
  
  CONCLUSIONS
  KLF4 may function as a tumor suppressor in cervical carcinoma by inhibiting cell growth and tumor formation.
authors.affiliation: Department of Reproductive Medicine, First Affiliated Hospital, Xi'an Jiaotong University of Medical School, Xi'an, People's Republic of China.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Yang
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Zheng
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis; D015536:Down-Regulation; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014183:Transplantation, Heterologous; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D050760:Cyclin-Dependent Kinase Inhibitor p27