title: Downregulation of the KLF4 transcription factor inhibits the proliferation and migration of canine mammary tumor cells.
abstract: Canine mammary tumor (CMT) is the most common neoplasm in female dogs, and over 50% of CMTs are diagnosed as malignant. Krüppel-like factor 4 (KLF4) is a member of the KLF family of transcription factors and is associated with cell proliferation, differentiation, migration, and apoptosis. Although the role of KLF4 is still controversial in various human cancers, KLF4 has been identified as an oncogene in human breast cancer. Moreover, high KLF4 expression is correlated with an aggressive phenotype in CMT. Therefore, investigating the function of KLF4 may help better understand the pathogenesis of CMT. In this study, partial sequences of canine KLF4 and KLF4 expression were identified in various normal canine tissues, as well as CMT cells and Madin-Darby canine kidney (MDCK) cells. Kenpaullone, a small molecule inhibitor of KLF4, downregulated KLF4 expression in CMT cells and reduced CMT cell proliferation, migration, and colony formation in soft agar. Kenpaullone treatment induced S and G2/M phase arrest in CMT and MDCK cells, and induced death in CMT cells, but not in MDCK cells. It was concluded that KLF4 is expressed in various normal canine tissues, and downregulation of KLF4 inhibited CMT cell proliferation and migration, and induced cell death. The results of this study suggest that KLF4 may represent a suitable therapeutic target for CMT therapy.
authors.affiliation: Department and Graduate Institute of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan.
authors.forename: Yung-Tien
authors.initials: YT
authors.lastname: Tien
authors.affiliation: Department and Graduate Institute of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan; Animal Cancer Center, National Taiwan University, Taipei, 10617, Taiwan.
authors.forename: Mei-Hsien
authors.initials: MH
authors.lastname: Chang
authors.affiliation: School of Medicine, Fu-Jen Catholic University, New Taipei City, 24202, Taiwan; Department of Pathology, St. Martin De Porres Hospital, Chiayi, 60069, Taiwan.
authors.forename: Pei-Yi
authors.initials: PY
authors.lastname: Chu
authors.affiliation: Department and Graduate Institute of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan; Animal Cancer Center, National Taiwan University, Taipei, 10617, Taiwan.
authors.forename: Chen-Si
authors.initials: CS
authors.lastname: Lin
authors.affiliation: Animal Cancer Center, National Taiwan University, Taipei, 10617, Taiwan; Graduate Institute of Molecular and Comparative Pathobiology, National Taiwan University, Taipei, 10617, Taiwan; National Taiwan University Veterinary Hospital, National Taiwan University, Taipei, 10617, Taiwan.
authors.forename: Chen-Hsuan
authors.initials: CH
authors.lastname: Liu
authors.affiliation: Department and Graduate Institute of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan; Animal Cancer Center, National Taiwan University, Taipei, 10617, Taiwan. Electronic address: Setaria11@gmail.com.
authors.forename: Albert T
authors.initials: AT
authors.lastname: Liao
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002465:Cell Movement; D049109:Cell Proliferation; D004283:Dog Diseases / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D007211:Indoles / Q000494:pharmacology; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D001552:Benzazepines; D007211:Indoles; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C119620:kenpaullone
keywords: Canine; Cell cycle; Kenpaullone; Krüppel-like factor 4 (KLF4); Mammary tumor