Runt-related transcription factor 2 in human colon carcinoma: A potent prognostic factor associated with estrogen receptor

Tomohiko Sase, Takashi Suzuki, Koh Miura, Kenichi Shiiba, Ikuro Sato, Yasuhiro Nakamura, Kiyoshi Takagi, Yoshiaki Onodera, Yasuhiro Miki, Mika Watanabe, Kazuyuki Ishida, Shinobu Ohnuma, Hiroyuki Sasaki, Ryuichiro Sato, Hideaki Karasawa, Chikashi Shibata, Michiaki Unno, Iwao Sasaki, Hironobu Sasano

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

Abstract

Runt-related transcription factor 2 (RUNX2) belongs to the RUNX family of heterodimeric transcription factors, and is mainly associated with osteogenesis. Previous in vitro studies demonstrated that RUNX2 increased the cell proliferation of mouse and rat colon carcinoma cells but the status of RUNX2 has remained unknown in human colon carcinoma. Therefore, we examined clinical significance and biological functions of RUNX2 in colon carcinoma. RUNX2 immunoreactivity was examined in 157 colon carcinoma tissues using immunohistochemistry. RUNX2 immunoreactivity was evaluated as percentage of positive carcinoma cells [i.e., labeling index (LI)]. We used SW480 and DLD-1 human colon carcinoma cells, expressing estrogen receptor-β (ER) in subsequent in vitro studies. RUNX2 immunoreactivity was detected in colon carcinoma cells, and the median value of RUNX2 LI was 67%. RUNX2 LI was significantly associated with Dukes' stage, liver metastasis and ERβ status. In addition, RUNX2 LI was significantly associated with adverse clinical outcome of the colon carcinoma patients, and turned out an independent prognostic factor following multivariate analysis. Results of in vitro studies demonstrated that both SW480 and DLD-1 cells transfected with small interfering RNA against RUNX2 significantly decreased their cell proliferation, migration and invasive properties. In addition, RUNX2 mRNA level was significantly decreased by ER antagonist in these two cells. These findings all suggest that RUNX2 is a potent prognostic factor in human colon carcinoma patients through the promotion of cell proliferation and invasion properties, and is at least partly upregulated by estrogen signals through ERβ of carcinoma cells.

Original languageEnglish
Pages (from-to)2284-2293
Number of pages10
JournalInternational Journal of Cancer
Volume131
Issue number10
DOIs
Publication statusPublished - 2012 Nov 15

Keywords

  • Runt-related transcription factor 2
  • colon carcinoma
  • estrogen receptor
  • immunohistochemistry
  • prognosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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