Overexpression of Evi-1 oncoprotein represses TGF-β signaling in colorectal cancer

Xiyun Deng, Yanna Cao, Yan Liu, Fazhi Li, Kamalanathan Sambandam, Srinivasan Rajaraman, Archibald S. Perkins, Alan P Fields, Mark R. Hellmich, Courtney M. Townsend, E Aubrey Thompson, Tien C. Ko

Research output: Contribution to journalArticle

16 Citations (Scopus)

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. © 2011 Wiley Periodicals, Inc.

Original languageEnglish (US)
Pages (from-to)255-264
Number of pages10
JournalMolecular Carcinogenesis
Volume52
Issue number4
DOIs
StatePublished - Apr 2013

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Virus Integration
Oncogene Proteins
Transforming Growth Factors
Colorectal Neoplasms
Colonic Neoplasms
Adenoma
Transfection
Colon
Carcinogenesis

Keywords

  • Colorectal cancer
  • Ecotropic virus integration site-1
  • Growth inhibition
  • Rapid amplification of cDNA ends
  • Smad proteins
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

Cite this

Deng, X., Cao, Y., Liu, Y., Li, F., Sambandam, K., Rajaraman, S., ... Ko, T. C. (2013). Overexpression of Evi-1 oncoprotein represses TGF-β signaling in colorectal cancer. Molecular Carcinogenesis, 52(4), 255-264. https://doi.org/10.1002/mc.21852

Overexpression of Evi-1 oncoprotein represses TGF-β signaling in colorectal cancer. / Deng, Xiyun; Cao, Yanna; Liu, Yan; Li, Fazhi; Sambandam, Kamalanathan; Rajaraman, Srinivasan; Perkins, Archibald S.; Fields, Alan P; Hellmich, Mark R.; Townsend, Courtney M.; Thompson, E Aubrey; Ko, Tien C.

In: Molecular Carcinogenesis, Vol. 52, No. 4, 04.2013, p. 255-264.

Research output: Contribution to journalArticle

Deng, X, Cao, Y, Liu, Y, Li, F, Sambandam, K, Rajaraman, S, Perkins, AS, Fields, AP, Hellmich, MR, Townsend, CM, Thompson, EA & Ko, TC 2013, 'Overexpression of Evi-1 oncoprotein represses TGF-β signaling in colorectal cancer', Molecular Carcinogenesis, vol. 52, no. 4, pp. 255-264. https://doi.org/10.1002/mc.21852
Deng, Xiyun ; Cao, Yanna ; Liu, Yan ; Li, Fazhi ; Sambandam, Kamalanathan ; Rajaraman, Srinivasan ; Perkins, Archibald S. ; Fields, Alan P ; Hellmich, Mark R. ; Townsend, Courtney M. ; Thompson, E Aubrey ; Ko, Tien C. / Overexpression of Evi-1 oncoprotein represses TGF-β signaling in colorectal cancer. In: Molecular Carcinogenesis. 2013 ; Vol. 52, No. 4. pp. 255-264.
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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. {\circledC} 2011 Wiley Periodicals, Inc.",
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