Coordinated modulation of the fibroblast growth factor dual receptor mechanism during transformation from human colon adenoma to carcinoma.

2.50
Hdl Handle:
http://hdl.handle.net/10541/91396
Title:
Coordinated modulation of the fibroblast growth factor dual receptor mechanism during transformation from human colon adenoma to carcinoma.
Authors:
Jayson, Gordon C ( 0000-0002-8515-8944 ) ; Vives, Corinne; Paraskeva, Christos; Schofield, Karen P; Coutts, Jacquie; Fleetwood, Alison; Gallagher, John T
Abstract:
Basic 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.
Affiliation:
Cancer Research Campaign, Department of Medical Oncology, Paterson Institute, Manchester, UK. GordonJayson@Compuserve.com
Citation:
Coordinated modulation of the fibroblast growth factor dual receptor mechanism during transformation from human colon adenoma to carcinoma. 1999, 82 (2):298-304 Int. J. Cancer
Journal:
International Journal of Cancer
Issue Date:
19-Jul-1999
URI:
http://hdl.handle.net/10541/91396
DOI:
10.1002/(SICI)1097-0215(19990719)82:2<298::AID-IJC23>3.0.CO;2-9
PubMed ID:
10389767
Type:
Article
Language:
en
ISSN:
0020-7136
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorJayson, Gordon Cen
dc.contributor.authorVives, Corinneen
dc.contributor.authorParaskeva, Christosen
dc.contributor.authorSchofield, Karen Pen
dc.contributor.authorCoutts, Jacquieen
dc.contributor.authorFleetwood, Alisonen
dc.contributor.authorGallagher, John Ten
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.en
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
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