Functional significance of Wnt inhibitory factor-1 gene in kidney cancer

Kazumori Kawakami, Hiroshi Hirata, Soichiro Yamamura, Nobuyuki Kikuno, Sharanjot Saini, Shahana Majid, Yuichiro Tanaka, Ken Kawamoto, Hideki Enokida, Masayuki Nakagawa, Rajvir Dahiya

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60 Scopus citations

Abstract

Wnt inhibitory factor-1 (WIF-1) has been identified as one of the secreted antagonists that bind Wnt protein. WIF-1 has been described as a tumor suppressor in various types of cancer. However, the molecular function of WIF-1 gene has never been examined in human renal cell carcinoma (RCC). Therefore, we hypothesized that WIF-1 functions as a tumor suppressor gene and overexpression of this gene may induce apoptosis and inhibit tumor growth in RCC cells. Immunohistochemistry and real-time reverse transcription-PCR revealed that WIF-1 was significantly downregulated in RCC samples and RCC cell lines, respectively. Bisulfite sequencing of the WIF-1 promoter region in RCC cell lines showed it to be densely methylated, whereas there was no methylation of WIF-1 promoter in normal kidney. Significant inhibition of cell growth and colony formation in WIF-1-transfected cells compared with controls were observed. WIF-1 transfection significantly induced apoptosis and suppressed in vivo tumor growth. Also, Wnt signaling activity and â-catenin expression were reduced by WIF-1 transfection. In conclusion, this is the first report documenting that the WIF-1 is downregulated by promoter methylation and functions as a tumor suppressor gene by inducing apoptosis in RCC cells.

Original languageEnglish (US)
Pages (from-to)8603-8610
Number of pages8
JournalCancer Research
Volume69
Issue number22
DOIs
StatePublished - Nov 15 2009
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kawakami, K., Hirata, H., Yamamura, S., Kikuno, N., Saini, S., Majid, S., Tanaka, Y., Kawamoto, K., Enokida, H., Nakagawa, M., & Dahiya, R. (2009). Functional significance of Wnt inhibitory factor-1 gene in kidney cancer. Cancer Research, 69(22), 8603-8610. https://doi.org/10.1158/0008-5472.CAN-09-2534