KLF10, transforming growth factor-β-inducible early gene 1, acts as a tumor suppressor

Abstract

Krüppel-like factor 10 (KLF10) has been suggested to be a putative tumor suppressor. In the present study, we generated KLF10 deficient mice to explore this hypothesis in vivo. KLF10 deficient mice exhibited increased predisposition to skin tumorigenesis and markedly accelerated papilloma development after DMBA/TPA treatment. On the other hand, KLF10 deficient keratinocytes showed increased proliferation and apoptosis. In colony formation assays after oncogenic H-Ras transfection, KLF10 deficient mouse embryonic fibroblasts (MEFs) yielded more colonies than wild-type MEFs. Furthermore, KLF10 dose-dependently activated p21(WAF1/CIP1) transcription, which was independent of p53 and Sp1 binding sites in p21(WAF1/CIP1) promoter. This study demonstrates that KLF10 is a tumor suppressor and that it targets p21(WAF1/CIP1) transcription.