KLF5 promotes cell proliferation and tumorigenesis through gene regulation and the TSU-Pr1 human bladder cancer cell line.
KLF5 is a transcription factor that plays important roles in multiple physical and pathological processes, including cell growth, cell cycle regulation, and angiogenesis. To better characterize KLF5 function in bladder carcinogenesis, we established stable TSU-Pr1 cell clones expressing different levels of KLF5. These clones were then characterized for cell growth, cell cycle progression, tumorigenesis, and alteration in gene expression. Overexpression of KLF5 promoted tumorigenesis of the TSU-Pr1 cancer cells in mice. Consistently, KLF5 increased G1 to S phase transition, which was accompanied by the upregulation of cyclin D1, phosphorylation of MAPK and Akt, and reduced protein levels for CDK inhibitors p27 and p15. Microarray analysis combined with expression verification in different cell systems identified a number of additional genes that are potentially regulated by KLF5, including HBP17, ITGA6, and RAIG1. These findings suggest that the KLF5 transcription factor plays an oncogenic role in the TSU-Pr1 bladder cancer cell line through the regulation of a subset of genes.
Chen
Ceshi
C
Winship Cancer Institute and Department of Oncology and Hematology, Emory University School of Medicine, Atlanta, GA, USA.
Benjamin
Michael S
MS
Sun
Xiaodong
X
Otto
Kristen B
KB
Guo
Peng
P
Dong
Xue-Yuan
XY
Bao
Yongde
Y
Zhou
Zhongmei
Z
Cheng
Xiaohong
X
Simons
Jonathan W
JW
Dong
Jin-Tang
JT
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002999:Clone Cells; D019938:Cyclin D1 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016196:S Phase / Q000235:genetics / Q000502:physiology; D014183:Transplantation, Heterologous; D047368:Tumor Burden; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors; D034741:RNA, Small Interfering; D019938:Cyclin D1; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases