Preferential expression of the third immunoglobulin-like domain of K-sam product provides keratinocyte growth factor-dependent growth in carcinoma cell lines.
Previously, we identified an amplified gene in a stomach cancer cell line, KATO-III, and designated it K-sam. This gene was later found to be identical with a gene for a receptor tyrosine kinase, bek/FGFR2. One of the characteristics of the K-sam gene is structural diversity of its transcripts; K-sam complementary DNA (cDNA) cloned from human brain (K-sam-I) has a completely different sequence at the third extracellular immunoglobulin-like domain as compared to that of the K-sam cDNA derived from KATO-III cells (K-sam-II). Recent study has revealed that this difference signifies a differential ligand affinity; the receptor encoded by the K-sam-I cDNA has a high affinity for basic fibroblast growth factor (bFGF), while the K-sam-II cDNA corresponds to a receptor with the high affinity for keratinocyte growth factor (KGF). Reverse transcription-polymerase chain reaction and RNA blot analysis showed that the K-sam-II-type transcript was present in carcinoma cell lines but not in any of the sarcoma cell lines examined. The K-sam-I-type transcript was expressed in both carcinoma and sarcoma cell lines. Furthermore, KGF enhanced the DNA synthesis of the esophageal cancer cells, TE-1, in a dose-dependent manner, while the effect of bFGF was not substantial. In contrast, the glioblastoma cell line, A-172, that expressed the bFGF receptor showed a mitogenic response to bFGF but not to KGF. These data suggest that KGF is a growth factor used preferentially in cancer cells, and this preference is based on the presence of the K-sam-II-type receptor in carcinoma cells but not in sarcoma cells due to alternative splicing.
Ishii
H
H
Genetics Division, National Cancer Center Research Institute, Tokyo, Japan.
Hattori
Y
Y
Itoh
H
H
Kishi
T
T
Yoshida
T
T
Sakamoto
H
H
Oh
H
H
Yoshida
S
S
Sugimura
T
T
Terada
M
M
D001483:Base Sequence; D002277:Carcinoma / Q000737:chemistry / Q000235:genetics*; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D051526:Fibroblast Growth Factor 10; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D015972:Gene Expression Regulation, Neoplastic; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D015347:RNA Probes; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis*; D012509:Sarcoma / Q000737:chemistry / Q000235:genetics*; D013724:Teratoma / Q000737:chemistry / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; C496453:FGF7 protein, human; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D015347:RNA Probes; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors