Oncogenic functions of secreted Frizzled-related protein 2 in human renal cancer

Soichiro Yamamura, Kazumori Kawakami, Hiroshi Hirata, Koji Ueno, Sharanjot Saini, Shahana Majid, Rajvir Dahiya

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

The secreted Frizzled-related proteins (sFRP) are modulators of the Wnt signaling pathway, which is involved in embryonic development and tumor progression. The functions of sFRP2 have not been studied in renal cancer. Transient transfection of sFRP2 promoted cell growth in renal carcinoma cells, whereby the largest effect was observed in A498 cells. To further study the functions of sFRP2 gene in renal carcinoma cells, we established A498 renal cancer cell lines, which stably expressed sFRP2. Stably expressed sFRP2 significantly promoted cell proliferation in vitro and in vivo tumor growth. The stably expressed sFRP2 cells were also found to have reduced UV-induced apoptosis and increased G2 phase of the cell cycle. The phosphorylation level at Ser33/37 /Thr41 of β-catenin was lower in the stable sFRP2 cell lines compared with the control cell line. sFRP2 significantly activated T-cell factor/lymphoid enhancer factor transcriptional activity. In the stable sFRP2 cell line, expression of c-Fos, Bcl2, Bcl-w, cyclin B2, and cyclin E2 genes was significantly increased and p53 expression was decreased. This is the first report documenting that sFRP2 activates the canonical Wnt pathway and promotes cell growth by evoking diverse signaling cascades in renal cancer cells. This study may provide better strategies for the management of renal cancer through regulation of sFRP2 pathways.

Original languageEnglish (US)
Pages (from-to)1680-1687
Number of pages8
JournalMolecular cancer therapeutics
Volume9
Issue number6
DOIs
StatePublished - Jun 1 2010
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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