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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2008-1-31
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/BMP4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Bmp4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 4,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/GPI-Linked Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Smad Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TDGF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tdgf1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1097-4652
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pubmed:author |
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pubmed:copyrightInfo |
(c) 2007 Wiley-Liss, Inc.
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pubmed:issnType |
Electronic
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pubmed:volume |
215
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
192-203
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:17941089-5' Flanking Region,
pubmed-meshheading:17941089-Animals,
pubmed-meshheading:17941089-Base Sequence,
pubmed-meshheading:17941089-Bone Morphogenetic Protein 4,
pubmed-meshheading:17941089-Bone Morphogenetic Proteins,
pubmed-meshheading:17941089-Cell Movement,
pubmed-meshheading:17941089-Cell Proliferation,
pubmed-meshheading:17941089-Colonic Neoplasms,
pubmed-meshheading:17941089-Embryonal Carcinoma Stem Cells,
pubmed-meshheading:17941089-Epidermal Growth Factor,
pubmed-meshheading:17941089-GPI-Linked Proteins,
pubmed-meshheading:17941089-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:17941089-Humans,
pubmed-meshheading:17941089-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:17941089-Membrane Glycoproteins,
pubmed-meshheading:17941089-Mice,
pubmed-meshheading:17941089-Molecular Sequence Data,
pubmed-meshheading:17941089-Mutation,
pubmed-meshheading:17941089-Neoplasm Proteins,
pubmed-meshheading:17941089-Promoter Regions, Genetic,
pubmed-meshheading:17941089-Protein Binding,
pubmed-meshheading:17941089-RNA, Messenger,
pubmed-meshheading:17941089-Smad Proteins,
pubmed-meshheading:17941089-Transforming Growth Factor beta1
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pubmed:year |
2008
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pubmed:articleTitle |
Regulation of human Cripto-1 gene expression by TGF-beta1 and BMP-4 in embryonal and colon cancer cells.
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pubmed: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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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Intramural
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