Document Detail


Regulation of human Cripto-1 gene expression by TGF-beta1 and BMP-4 in embryonal and colon cancer cells.
MedLine Citation:
PMID:  17941089     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Mario Mancino; Luigi Strizzi; Christian Wechselberger; Kazuhide Watanabe; Monica Gonzales; Shin Hamada; Nicola Normanno; David S Salomon; Caterina Bianco
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  215     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-01-31     Completed Date:  2008-02-19     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  192-203     Citation Subset:  IM    
Copyright Information:
(c) 2007 Wiley-Liss, Inc.
Affiliation:
Tumor Growth Factor Section, Mammary Biology and Tumorigenesis Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20832, USA.
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MeSH Terms
Descriptor/Qualifier:
5' Flanking Region
Animals
Base Sequence
Bone Morphogenetic Protein 4
Bone Morphogenetic Proteins / pharmacology*
Cell Movement / drug effects
Cell Proliferation / drug effects
Colonic Neoplasms / genetics*,  pathology
Embryonal Carcinoma Stem Cells / metabolism*,  pathology
Epidermal Growth Factor / deficiency,  genetics*,  metabolism
Gene Expression Regulation, Neoplastic / drug effects*
Humans
Membrane Glycoproteins / deficiency,  genetics*,  metabolism
Mice
Molecular Sequence Data
Mutation / genetics
Neoplasm Proteins / deficiency,  genetics*,  metabolism
Promoter Regions, Genetic
Protein Binding / drug effects
RNA, Messenger / genetics,  metabolism
Smad Proteins / metabolism
Transforming Growth Factor beta1 / pharmacology*
Chemical
Reg. No./Substance:
0/BMP4 protein, human; 0/Bmp4 protein, mouse; 0/Bone Morphogenetic Protein 4; 0/Bone Morphogenetic Proteins; 0/Membrane Glycoproteins; 0/Neoplasm Proteins; 0/RNA, Messenger; 0/Smad Proteins; 0/TDGF1 protein, human; 0/Tdgf1 protein, mouse; 0/Transforming Growth Factor beta1; 62229-50-9/Epidermal Growth Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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