Up-regulation and co-expression of fibroblast growth factor receptors in human gastric cancer

Citation
Ey. Shin et al., Up-regulation and co-expression of fibroblast growth factor receptors in human gastric cancer, J CANC RES, 126(9), 2000, pp. 519-528
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
ISSN journal
0171-5216 → ACNP
Volume
126
Issue
9
Year of publication
2000
Pages
519 - 528
Database
ISI
SICI code
0171-5216(200009)126:9<519:UACOFG>2.0.ZU;2-C
Abstract
Fibroblast growth factor (FGF), a key regulatory factor of cell growth and differentiation, is involved in embryonic development, angiogenesis, and tu morigenesis. To date, four different FGF receptors (FGFRs) have been cloned and characterized. We examined the expression of four FGFRs in human gastr ic cancer tissues and cell lines using Northern analysis, ribonuclease prot ection assay, and immunohistochemistry. The mRNAs of FGFR-1 (10/14), FGFR-2 (9/14), and FGFR-4 (9/14) were up-regulated in cancer compared with normal tissues. FGFR-3 mRNAs were barely detectable in both normal and cancer tis sues. These FGFR mRNAs were co-expressed in various combinations of two or three in the same tissue. Immunohistochemistry confirmed specific staining of multiple FGFRs, except FGFR-3, in the cancer specimens. To investigate t he functional significance of FGFR co-expression we examined the invasive p roperty of SNU-16 cells, which exhibited gene amplification of FGFR-2, -3, and -4 as well as over-expression of keratinocyte growth factor receptor (K GFR), a splice variant of FGFR-2, and FGFR-4 mRNA. KGF plus acidic FGF (aFG F), KGF, and aFGF treatment enhanced the invasive potential of SNU-16 cells over the control by 100%, 107%, and 47%, respectively, indicating that nei ther additive nor synergistic effect was induced by stimulation with aFGF p lus KGF. These results suggest that co-expression of FGFRs in Various combi nations may cause subtle changes in the progression of gastric cancer.