KLF4 and KLF5 regulate proliferation, apoptosis and invasion in esophageal cancer cells.
KLF4 and KLF5, members of the KLF family of transcription factors, play key roles in proliferation, differentiation, and carcinogenesis in a number of gastrointestinal tissues. While KLF4 is expressed in differentiating epithelial cells, KLF5 is found in proliferating cells of the gastrointestinal tract, including the esophagus. KLF4 regulates a number of genes vital for esophageal epithelial differentiation, and decreased expression of KLF4 is seen in esophageal squamous cancers. Nonetheless, the roles of KLF4 and KLF5 in esophageal tumor progression are not known. Here, using TE2 cells stably infected with retroviral vectors to express KLF4 or KLF5, we demonstrate that KLF4 and KLF5 are key players in a number of cellular processes critical for esophageal carcinogenesis. TE2 cells, derived from a patient with poorly differentiated esophageal squamous cancer, normally lack KLF4 and KLF5. Expression of KLF5 in TE2 cells inhibits proliferation, and both KLF4 and KLF5 decrease viability after treatment with hydrogen peroxide and increase anoikis. In response to DNA damage from UV irradiation, viability is decreased in KLF5 but not KLF4 infected cells. Both KLF4 and KLF5 upregulate the cdk inhibitor p21(waf1/cip1) following UV irradiation, but the pro-apoptotic protein BAX is markedly induced only by KLF5. Thus KLF4 may preferentially activate DNA repair pathways while KLF5 induces both DNA repair and apoptosis after UV irradiation. Expression of KLF4 or KLF5 in TE2 cells also inhibits invasion, consistent with a role for each in preventing tumor metastasis. In summary, KLF4 and KLF5 regulate esophageal carcinogenesis by affecting proliferation, apoptosis, and invasion.
Yang
Yizeng
Y
Department of Medicine, Gastroenterology Division, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania 19104-6144, USA.
Goldstein
Bree G
BG
Chao
Hann-Hsiang
HH
Katz
Jonathan P
JP
D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000502:physiology*; D009361:Neoplasm Invasiveness / Q000517:prevention & control
C000715467:KLF4 protein, human; C492214:KLF5 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors