title: Overexpression of Evi-1 oncoprotein represses TGF-β signaling in colorectal cancer.
abstract: 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.
authors.affiliation: Department of Surgery, The University of Texas Health Science Center, Houston, Texas.
authors.forename: Xiyun
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Surgery, The University of Texas Health Science Center, Houston, Texas.
authors.forename: Yanna
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Mayo Clinic, Jacksonville, Florida.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Surgery, The University of Texas Medical Branch, Galveston, Texas.
authors.forename: Fazhi
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Surgery, The University of Texas Medical Branch, Galveston, Texas.
authors.forename: Kamalanathan
authors.initials: K
authors.lastname: Sambandam
authors.affiliation: Department of Surgery, The University of Texas Medical Branch, Galveston, Texas.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Rajaraman
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Archibald S
authors.initials: AS
authors.lastname: Perkins
authors.affiliation: Mayo Clinic, Jacksonville, Florida.
authors.forename: Alan P
authors.initials: AP
authors.lastname: Fields
authors.affiliation: Department of Surgery, The University of Texas Medical Branch, Galveston, Texas.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Hellmich
authors.affiliation: Department of Surgery, The University of Texas Medical Branch, Galveston, Texas.
authors.forename: Courtney M
authors.initials: CM
authors.lastname: Townsend
authors.affiliation: Mayo Clinic, Jacksonville, Florida.
authors.forename: E Aubrey
authors.initials: EA
authors.lastname: Thompson
authors.affiliation: Department of Surgery, The University of Texas Health Science Center, Houston, Texas.|Department of Surgery, The University of Texas Medical Branch, Galveston, Texas.
authors.forename: Tien C
authors.initials: TC
authors.lastname: Ko
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000074008:MDS1 and EVI1 Complex Locus Protein; D051379:Mice; D011401:Promoter Regions, Genetic; D011519:Proto-Oncogenes / Q000235:genetics*; D012007:Rectum / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; C499305:Mecom protein, mouse; D014157:Transcription Factors; D016212:Transforming Growth Factor beta