Regulation of human Cripto-1 gene expression by TGF-beta1 and BMP-4 in embryonal and colon cancer cells.

Regulation of human Cripto-1 gene expression by TGF-beta1 and BMP-4 in embryonal and colon cancer cells. Research Abstract Details 

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Regulation of human Cripto-1 gene expression by TGF-beta1 and BMP-4 in embryonal and colon cancer cells. Abstract Text:

Mario Mancino,Luigi Strizzi,Christian Wechselberger,Kazuhide Watanabe,Monica Gonzales,Shin Hamada,Nicola Normanno,David S Salomon,Caterina Bianco,Mario Mancino,Luigi Strizzi,Christian Wechselberger,Kazuhide Watanabe,Monica Gonzales,Shin Hamada,Nicola Normanno,David S Salomon,Caterina Bianco,

Human Cripto-1 (CR-1) is a cell membrane protein that is overexpressed in several different types of human carcinomas. In the present study we investigated the mechanisms that regulate the expression of CR-1 gene in cancer cells. We cloned a 2,481 bp 5'-flanking region of the human CR-1 gene into a luciferase reporter vector and transfected NTERA-2 human embryonal carcinoma cells and LS174-T colon cancer cells to test for promoter activity. Activity of CR-1 promoter in both cell lines was modulated by two TGF-beta family members, TGF-beta1 and BMP-4. In particular, TGF-beta1 significantly up-regulated CR-1 promoter activity, whereas a dramatic reduction in CR-1 promoter activity was observed with BMP-4 in NTERA-2 and LS174-T cells. Changes in the CR-1 promoter activity following TGF-beta1 and BMP-4 treatments correlated with changes in CR-1 mRNA and protein expression in NTERA-2 and LS174-T cells. We also identified three Smad binding elements (SBEs) within the CR-1 promoter and point mutation of SBE1 (-2,197/-2,189) significantly reduced response of the CR-1 promoter to both TGF-beta1 and BMP-4 in NTERA-2 and LS174-T cells. Chromatin immunoprecipitation assay also demonstrated binding of Smad-4 to a CR-1 promoter DNA sequence containing SBE1 in LS174-T cells. Finally, BMP-4 inhibited migration of LS174-T cells and F9 mouse embryonal carcinoma cells by downregulation of CR-1 protein. In conclusion, these results suggest a differential modulation of CR-1 gene expression in embryonal and colon cancer cells by two different members of the TGF-beta family.

Regulation of human Cripto-1 gene expression by TGF-beta1 and BMP-4 in embryonal and colon cancer cells. Publishing Authors By Initials

M Mancino,L Strizzi,C Wechselberger,K Watanabe,M Gonzales,S Hamada,N Normanno,DS Salomon,C Bianco,M Mancino,L Strizzi,C Wechselberger,K Watanabe,M Gonzales,S Hamada,N Normanno,DS Salomon,C Bianco,

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Regulation of human Cripto-1 gene expression by TGF-beta1 and BMP-4 in embryonal and colon cancer cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of cellular physiology

VOLUME: 215

Page Numbers: 192-203

Journal Abbreviation: J. Cell. Physiol.

ISSN: 1097-4652

DAY: 31

MONTH: Apr

YEAR: 2008

Regulation of human Cripto-1 gene expression by TGF-beta1 and BMP-4 in embryonal and colon cancer cells. Information

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LANGUAGE: eng

NlmUniqueID: 50222

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Grant and Affiliation Information for Regulation of human Cripto-1 gene expression by TGF-beta1 and BMP-4 in embryonal and colon cancer cells.

AFFILIATION: Tumor Growth Factor Section, Mammary Biology and Tumorigenesis Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20832, USA.

Country: United States

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MEDLINETA: J Cell Physiol

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