RESUMEN
We have identified a novel fibroblast growth factor, FGF-19, the most distant member of the FGF family described to date. FGF-19 is a high affinity, heparin dependent ligand for FGFR4 and is the first member of the FGF family to show exclusive binding to FGFR4. Human FGF-19 maps to chromosome 11 q13.1, a region associated with an osteoporosis-pseudoglioma syndrome of skeletal and retinal defects. FGF-19 message is expressed in several tissues including fetal cartilage, skin, and retina, as well as adult gall bladder and is overexpressed in a colon adenocarcinoma cell line.
Asunto(s)
Factores de Crecimiento de Fibroblastos/genética , Factores de Crecimiento de Fibroblastos/metabolismo , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Adenocarcinoma , Secuencia de Aminoácidos , Animales , Secuencia de Bases , División Celular , Línea Celular , Cromosomas Humanos Par 11/genética , Clonación Molecular , Neoplasias Colorrectales , Factores de Crecimiento de Fibroblastos/química , Expresión Génica , Heparina/farmacología , Humanos , Datos de Secuencia Molecular , Filogenia , Mapeo Físico de Cromosoma , Unión Proteica/efectos de los fármacos , Señales de Clasificación de Proteína , ARN Mensajero/análisis , ARN Mensajero/genética , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos , Receptores de Factores de Crecimiento de Fibroblastos/genética , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/metabolismo , Retina/embriología , Retina/metabolismo , Alineación de Secuencia , Síndrome , Células Tumorales CultivadasRESUMEN
Wnt family members are critical to many developmental processes, and components of the Wnt signaling pathway have been linked to tumorigenesis in familial and sporadic colon carcinomas. Here we report the identification of two genes, WISP-1 and WISP-2, that are up-regulated in the mouse mammary epithelial cell line C57MG transformed by Wnt-1, but not by Wnt-4. Together with a third related gene, WISP-3, these proteins define a subfamily of the connective tissue growth factor family. Two distinct systems demonstrated WISP induction to be associated with the expression of Wnt-1. These included (i) C57MG cells infected with a Wnt-1 retroviral vector or expressing Wnt-1 under the control of a tetracyline repressible promoter, and (ii) Wnt-1 transgenic mice. The WISP-1 gene was localized to human chromosome 8q24.1-8q24.3. WISP-1 genomic DNA was amplified in colon cancer cell lines and in human colon tumors and its RNA overexpressed (2- to >30-fold) in 84% of the tumors examined compared with patient-matched normal mucosa. WISP-3 mapped to chromosome 6q22-6q23 and also was overexpressed (4- to >40-fold) in 63% of the colon tumors analyzed. In contrast, WISP-2 mapped to human chromosome 20q12-20q13 and its DNA was amplified, but RNA expression was reduced (2- to >30-fold) in 79% of the tumors. These results suggest that the WISP genes may be downstream of Wnt-1 signaling and that aberrant levels of WISP expression in colon cancer may play a role in colon tumorigenesis.