Growth inhibitory effect of Krüppel-like factor 6 on human prostatic carcinoma and renal carcinoma cell lines.
Kidney and prostate cancers are leading causes of death in the world, and accumulating evidence suggests that tumor suppressor gene, Krüppel-like factor 6 (KLF6), plays an important role in both the development and the progression of cancer. However, the effect of wild type KLF6 (wtKLF6) on the growth potential of renal carcinoma cells has not been examined. In the present study, we therefore introduced wtKLF6 gene into a prostatic carcinoma derived cell line, DU145, and a renal carcinoma derived cell line, OS-RC-2, and have established DU145-KLF6 and OS-RC-2-KLF6 cell lines, both of which stably over-express KLF6. Compared with vector-transfected cell lines (control cells), the wtKLF6-transfected cell lines showed the lower proliferation capacity (p < 0.01) and higher percentages of cells with apoptotic signals (p < 0.01). Moreover, the KLF6-overexpressed cell lines showed significant increases in the cell population at G0/G1 phase and significant decreases in the cell population at S and G2/M phases. There was no significant difference in the results of the cell cycle analysis between the two KLF6-overexpressed cell lines, DU145-KLF6 and OS-RC-2-KLF6. The cyclin-dependent kinase inhibitor p21 as a transcriptional target of the KLF6 gene was also studied. The expression levels of p21 mRNA and protein were up-regulated in both KLF6-overexpressed cell lines. These results indicate that the wtKLF6 gene effectively inhibited the growth of the prostatic carcinoma DU145 and renal carcinoma OS-RC-2 cell lines, probably through up-regulation of p21. Thus, KLF6 may represent a novel therapeutic target for inhibiting prostate and renal cancer.
Cheng
Xian-Feng
XF
Department of Urology, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Li
Di
D
Zhuang
Min
M
Chen
Zhao-Yan
ZY
Lu
De-Xiang
DX
Hattori
Toshio
T
D000230:Adenocarcinoma / Q000473:pathology*; D017209:Apoptosis; D002292:Carcinoma, Renal Cell / Q000473:pathology*; D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor / Q000166:cytology / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology*; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D011471:Prostatic Neoplasms / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000502:physiology; D014158:Transcription, Genetic; D014162:Transfection
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C105465:KLF6 protein, human; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins