Tumor suppressor activity of KLF6 mediated by downregulation of the PTTG1 oncogene.
The tumor suppressor Kruppel-like factor 6 (KLF6) is frequently inactivated in hepatocellular carcinoma (HCC). To unearth downstream transcriptional targets of KLF6, cDNA microarray analysis of whole liver was compared between KLF6+/+ and KLF6+/- mice. Pituitary tumor transforming gene 1 (PTTG1), an oncogene, was the most up-regulated transcript in KLF6+/- liver. In human HCCs, KLF6 mRNA was significantly decreased, associated with increased PTTG1. In HepG2, KLF6 transcriptionally repressed PTTG1 by direct promoter interaction. Whereas KLF6 downregulation by siRNA increased HepG2 proliferation, siRNA to PTTG1 was anti-proliferative. PTTG1 downregulation represents a novel tumor suppressor pathway of KLF6.
Lee
Ursula E
UE
Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Ghiassi-Nejad
Zahra
Z
Paris
Andrew J
AJ
Yea
Steven
S
Narla
Goutham
G
Walsh
Martin
M
Friedman
Scott L
SL
D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D006801:Humans; D066298:In Vitro Techniques; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064249:Securin
C491358:Klf6 protein, mouse; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human