title: Runt-related transcription factor 2 in human colon carcinoma: a potent prognostic factor associated with estrogen receptor.
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.
authors.affiliation: Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Sase
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Koh
authors.initials: K
authors.lastname: Miura
authors.forename: Kenichi
authors.initials: K
authors.lastname: Shiiba
authors.forename: Ikuro
authors.initials: I
authors.lastname: Sato
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takagi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Onodera
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miki
authors.forename: Mika
authors.initials: M
authors.lastname: Watanabe
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ishida
authors.forename: Shinobu
authors.initials: S
authors.lastname: Ohnuma
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sasaki
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Sato
authors.forename: Hideaki
authors.initials: H
authors.lastname: Karasawa
authors.forename: Chikashi
authors.initials: C
authors.lastname: Shibata
authors.forename: Michiaki
authors.initials: M
authors.lastname: Unno
authors.forename: Iwao
authors.initials: I
authors.lastname: Sasaki
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D021381:Protein Transport; D034622:RNA Interference
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D047629:Estrogen Receptor beta; C493709:RUNX2 protein, human