Up-regulation and co-expression of fibroblast growth factor receptors in human gastric cancer.
Fibroblast growth factor (FGF), a key regulatory factor of cell growth and differentiation, is involved in embryonic development, angiogenesis, and tumorigenesis. To date, four different FGF receptors (FGFRs) have been cloned and characterized. We examined the expression of four FGFRs in human gastric cancer tissues and cell lines using Northern analysis, ribonuclease protection 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 tissues. 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 the functional significance of FGFR co-expression we examined the invasive property of SNU-16 cells, which exhibited gene amplification of FGFR-2, -3, and -4 as well as over-expression of keratinocyte growth factor receptor (KGFR), a splice variant of FGFR-2, and FGFR-4 mRNA. KGF plus acidic FGF (aFGF), KGF, and aFGF treatment enhanced the invasive potential of SNU-16 cells over the control by 100%, 107%, and 47%, respectively, indicating that neither additive nor synergistic effect was induced by stimulation with aFGF plus KGF. These results suggest that co-expression of FGFRs in various combinations may cause subtle changes in the progression of gastric cancer.
Shin
E Y
EY
Department of Biochemistry, Pathology, and Surgery, College of Medicine, Chungbuk National University, Cheongju, Korea.
Lee
B H
BH
Yang
J H
JH
Shin
K S
KS
Lee
G K
GK
Yun
H Y
HY
Song
Y J
YJ
Park
S C
SC
Kim
E G
EG
D017398:Alternative Splicing; D015152:Blotting, Northern; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D005784:Gene Amplification; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
C496453:FGF7 protein, human; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D020033:Protein Isoforms; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor; D016220:Fibroblast Growth Factor 1; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; C496348:FGFR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor