title: 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.
authors.affiliation: Center for Agricultural Biomaterials, Seoul National University, Seoul 151-921, South Korea.
authors.forename: Ki-Duk
authors.initials: KD
authors.lastname: Song
authors.forename: Duk-Jung
authors.initials: DJ
authors.lastname: Kim
authors.forename: Jong Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Cheol-Heui
authors.initials: CH
authors.lastname: Yun
authors.forename: Woon Kyu
authors.initials: WK
authors.lastname: Lee
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051765:Early Growth Response Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010212:Papilloma / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic; D011725:Pyridines / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015127:9,10-Dimethyl-1,2-benzanthracene; D002273:Carcinogens; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D051765:Early Growth Response Transcription Factors; D051741:Kruppel-Like Transcription Factors; D011725:Pyridines; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C493957:Cdkn1a protein, mouse; C569958:KLF10 protein, mouse; C431843:tris(2-pyridylmethyl)amine