Knockdown of c-Fos suppresses the growth of human colon carcinoma cells in athymic mice

Manoj K. Pandey, Guangming Liu, Timothy K. Cooper, Kathleen M. Mulder

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Here we have investigated whether inhibition of c-Fos expression in RKO human colon carcinoma cells (HCCCs) would result in reduced TGFβ1 expression and suppression of tumor growth in athymic mice. We stably transfected RKO cells with c-Fos small interfering RNA (siRNA) or with the corresponding control siRNA. Using these stable cell lines, we demonstrated that siRNA-c-Fos significantly suppressed both AP-1 binding, promoter reporter activity at the proximal AP-1 site in the TGFβ1 promoter, and TGFβ1 production. Further, we established colon cancer xenografts with each of RKO-siRNA-EV, RKO-siRNA-Ctrl and RKO-siRNA-c-Fos cells. By 24 days, the tumor size of RKO-siRNA-c-Fos xenografts was 40% that of either RKO-EV or RKO-siRNA-Ctrl. Immunohistochemistry (IHC) of tumor xenografts demonstrated that siRNA-c-Fos significantly blocked c-Fos expression, and consequently expression of TGFβ1. However, expression of TGFβ2 and TGFβ3 were unaffected. Overall, our results demonstrate that blockade of TGFβ1 production by siRNA-c-Fos effectively suppressed tumor growth in vivo.

Original languageEnglish (US)
Pages (from-to)213-222
Number of pages10
JournalInternational Journal of Cancer
Volume130
Issue number1
DOIs
StatePublished - Jan 11 2012

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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