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dc.contributor.authorJayson, Gordon C
dc.contributor.authorVives, Corinne
dc.contributor.authorParaskeva, Christos
dc.contributor.authorSchofield, Karen P
dc.contributor.authorCoutts, Jacquie
dc.contributor.authorFleetwood, Alison
dc.contributor.authorGallagher, John T
dc.date.accessioned2010-02-08T15:32:47Z
dc.date.available2010-02-08T15:32:47Z
dc.date.issued1999-07-19
dc.identifier.citationCoordinated modulation of the fibroblast growth factor dual receptor mechanism during transformation from human colon adenoma to carcinoma. 1999, 82 (2):298-304 Int. J. Canceren
dc.identifier.issn0020-7136
dc.identifier.pmid10389767
dc.identifier.doi10.1002/(SICI)1097-0215(19990719)82:2<298::AID-IJC23>3.0.CO;2-9
dc.identifier.urihttp://hdl.handle.net/10541/91396
dc.description.abstractBasic fibroblast growth factor (bFGF) is dependent on heparan sulphate for its ability to activate the cell surface signal transducing receptor. We have investigated the FGF dual receptor mechanism in a novel model of the transformation from human colon adenoma to carcinoma in vitro. Reverse transcription-polymerase chain reaction showed that mRNA for FGF receptors 1 and 2 were expressed in both the adenoma and carcinoma cells whereas immunocytochemistry showed that the expression of the FGF R1 was reduced significantly in the carcinoma cells. We have reported previously that the composition and sequence of human colon adenoma and carcinoma heparan sulphate (HS) differ in a defined and specific manner. The functional significance of these changes was assessed by affinity co-electrophoresis, which showed that the affinity of adenoma HS for bFGF was 10-fold greater than that of the carcinoma HS (Kd 220 nM vs. 2493 nM, respectively). In addition, Northern studies of the expression of syndecan 1 and 4 mRNA showed that proteoglycan core protein expression was reduced significantly in the carcinoma cells. These findings were associated with a reduced biological response to bFGF in the carcinoma cells that could be partially reversed by the addition of exogenous heparin, suggesting that both the proteoglycan and signal transducing receptor control the cells' response to bFGF.
dc.language.isoenen
dc.subjectColonic Canceren
dc.subjectCancerous Gene Expression Regulationen
dc.subjectCancer Proteinsen
dc.subjectCancer RNAen
dc.subjectCultured Tumour Cellsen
dc.subject.meshAdenoma
dc.subject.meshCarcinoma
dc.subject.meshColonic Neoplasms
dc.subject.meshDisease Progression
dc.subject.meshDown-Regulation
dc.subject.meshFibroblast Growth Factor 2
dc.subject.meshFibroblast Growth Factors
dc.subject.meshGene Expression Regulation, Neoplastic
dc.subject.meshHeparin
dc.subject.meshHeparitin Sulfate
dc.subject.meshHumans
dc.subject.meshNeoplasm Proteins
dc.subject.meshProteoglycans
dc.subject.meshRNA, Messenger
dc.subject.meshRNA, Neoplasm
dc.subject.meshReceptor Protein-Tyrosine Kinases
dc.subject.meshReceptor, Fibroblast Growth Factor, Type 1
dc.subject.meshReceptor, Fibroblast Growth Factor, Type 2
dc.subject.meshReceptors, Fibroblast Growth Factor
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction
dc.subject.meshSignal Transduction
dc.subject.meshTumor Cells, Cultured
dc.titleCoordinated modulation of the fibroblast growth factor dual receptor mechanism during transformation from human colon adenoma to carcinoma.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign, Department of Medical Oncology, Paterson Institute, Manchester, UK. GordonJayson@Compuserve.comen
dc.identifier.journalInternational Journal of Canceren
html.description.abstractBasic fibroblast growth factor (bFGF) is dependent on heparan sulphate for its ability to activate the cell surface signal transducing receptor. We have investigated the FGF dual receptor mechanism in a novel model of the transformation from human colon adenoma to carcinoma in vitro. Reverse transcription-polymerase chain reaction showed that mRNA for FGF receptors 1 and 2 were expressed in both the adenoma and carcinoma cells whereas immunocytochemistry showed that the expression of the FGF R1 was reduced significantly in the carcinoma cells. We have reported previously that the composition and sequence of human colon adenoma and carcinoma heparan sulphate (HS) differ in a defined and specific manner. The functional significance of these changes was assessed by affinity co-electrophoresis, which showed that the affinity of adenoma HS for bFGF was 10-fold greater than that of the carcinoma HS (Kd 220 nM vs. 2493 nM, respectively). In addition, Northern studies of the expression of syndecan 1 and 4 mRNA showed that proteoglycan core protein expression was reduced significantly in the carcinoma cells. These findings were associated with a reduced biological response to bFGF in the carcinoma cells that could be partially reversed by the addition of exogenous heparin, suggesting that both the proteoglycan and signal transducing receptor control the cells' response to bFGF.


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