The zinc finger transcription factor Krüppel-like factor 4 (KLF4) has been implicated in both tumor suppression and progression. However, its function in pancreatic cancer has not been well characterized. Here, we show that pancreatic cancer cell lines expressed various levels of KLF4 RNA and protein. Ectopic expression of KLF4 by FG and BxPC-3 pancreatic cancer cells resulted in cell cycle arrest and marked inhibition of cell growth in vitro and attenuation of tumor growth and metastasis in an orthotopic mouse model. Overexpression of KLF4 also led to significant induction of p27Kip1 expression, at both the RNA and protein levels, in a dose-and time-dependent manner, indicating that KLF4 transcriptionally regulates the expression of p27 Kip1. Chromatin immunoprecipitation assays consistently showed that KLF4 protein physically interacts with the p27 Kip1 promoter. Promoter deletion and point mutation analyses indicated that a region between nucleotides À435 and À60 of the p27 Kip1 promoter and intact of the three KLF4-binding sites within that region were required for the full induction of p27 Kip1 promoter activity by KLF4. Our findings suggest that KLF4 transactivates p27Kip1 expression and inhibits the growth and metastasis of human pancreatic cancer. [Cancer Res 2008;68(12):4631-9]

Supplementary Figure 3 from Krüppel-like Factor 4 Induces <i>p27^Kip1</i> Expression in and Suppresses the Growth and Metastasis of Human Pancreatic Cancer Cells

Supplementary Figure 5 from Krüppel-like Factor 4 Induces <i>p27^Kip1</i> Expression in and Suppresses the Growth and Metastasis of Human Pancreatic Cancer Cells

Supplementary Figure 2 from Krüppel-like Factor 4 Induces <i>p27^Kip1</i> Expression in and Suppresses the Growth and Metastasis of Human Pancreatic Cancer Cells

Supplementary Figure 4 from Krüppel-like Factor 4 Induces <i>p27^Kip1</i> Expression in and Suppresses the Growth and Metastasis of Human Pancreatic Cancer Cells