TY - JOUR
T1 - Overexpression of Evi-1 oncoprotein represses TGF-β signaling in colorectal cancer
AU - Deng, Xiyun
AU - Cao, Yanna
AU - Liu, Yan
AU - Li, Fazhi
AU - Sambandam, Kamalanathan
AU - Rajaraman, Srinivasan
AU - Perkins, Archibald S.
AU - Fields, Alan P.
AU - Hellmich, Mark R.
AU - Townsend, Courtney M.
AU - Thompson, E. Aubrey
AU - Ko, Tien C.
PY - 2013/4
Y1 - 2013/4
N2 - Human colorectal cancer (CRC) cells are resistant to the anti-proliferative effect of transforming growth factor-β (TGF-β), suggesting that disruption of TGF-β signaling plays an important role in colorectal carcinogenesis. Ecotropic virus integration site-1 (Evi-1) oncoprotein represses TGF-β signaling by interacting with Smads, but its role in CRC has not been established. The purpose of this study is to determine whether Evi-1 plays role(s) in CRCs and to characterize Evi-1 transcript(s) in CRCs. Evi-1 was overexpressed in 53% of human CRC samples, 100% of colon adenoma samples, and 100% of human colon cancer cell lines tested. Using 5′ RACE, we cloned a novel Evi-1 transcript (Evi-1e) from a human CRC tissue and found that this novel transcript was expressed at a higher level in CRC tissues than in normal tissues and was the major Evi-1 transcript in CRCs. Transient Evi-1 transfection inhibited TGF-β-induced transcriptional activity and reversed the growth inhibitory effect of TGF-β in MC-26 mouse colon cancer cells. In conclusion, we have identified overexpression of Evi-1 oncoprotein as a novel mechanism by which a subset of human CRCs may escape TGF-β regulation. We have also identified a novel Evi-1 transcript, Evi-1e, as the major Evi-1 transcript expressed in human CRCs. © 2011 Wiley Periodicals, Inc.
AB - Human colorectal cancer (CRC) cells are resistant to the anti-proliferative effect of transforming growth factor-β (TGF-β), suggesting that disruption of TGF-β signaling plays an important role in colorectal carcinogenesis. Ecotropic virus integration site-1 (Evi-1) oncoprotein represses TGF-β signaling by interacting with Smads, but its role in CRC has not been established. The purpose of this study is to determine whether Evi-1 plays role(s) in CRCs and to characterize Evi-1 transcript(s) in CRCs. Evi-1 was overexpressed in 53% of human CRC samples, 100% of colon adenoma samples, and 100% of human colon cancer cell lines tested. Using 5′ RACE, we cloned a novel Evi-1 transcript (Evi-1e) from a human CRC tissue and found that this novel transcript was expressed at a higher level in CRC tissues than in normal tissues and was the major Evi-1 transcript in CRCs. Transient Evi-1 transfection inhibited TGF-β-induced transcriptional activity and reversed the growth inhibitory effect of TGF-β in MC-26 mouse colon cancer cells. In conclusion, we have identified overexpression of Evi-1 oncoprotein as a novel mechanism by which a subset of human CRCs may escape TGF-β regulation. We have also identified a novel Evi-1 transcript, Evi-1e, as the major Evi-1 transcript expressed in human CRCs. © 2011 Wiley Periodicals, Inc.
KW - Colorectal cancer
KW - Ecotropic virus integration site-1
KW - Growth inhibition
KW - Rapid amplification of cDNA ends
KW - Smad proteins
KW - Transforming growth factor-β
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U2 - 10.1002/mc.21852
DO - 10.1002/mc.21852
M3 - Article
C2 - 22161860
AN - SCOPUS:84877273370
SN - 0899-1987
VL - 52
SP - 255
EP - 264
JO - Molecular Carcinogenesis
JF - Molecular Carcinogenesis
IS - 4
ER -