Sj. Feng et al., FIBROBLAST GROWTH-FACTOR RECEPTOR-2 LIMITS AND RECEPTOR-1 ACCELERATESTUMORIGENICITY OF PROSTATE EPITHELIAL-CELLS, Cancer research, 57(23), 1997, pp. 5369-5378
Progressive loss of the differentiated phenotype and communication wit
h stroma accompanies the transition of nonmalignant rat prostate epith
elial cells to anaplastic, malignant tumors. Here me show that cell su
rface expression of the fibroblast growth factor receptor 2 (FGFR2) ty
rosine kinase is reduced in malignant tumor cell populations (type TI)
and undetectable at the mRNA level in 30% of cells, This is in additi
on to the irreversible loss by splice switching of the FGFR2 ectodomai
n that abrogates response to FGF-7 and homologues from the stroma, One
hundred % of type II malignant cells express FGFR1, which is normally
expressed in the stroma. Expression of the FGFR1 kinase in premaligna
nt type I tumor epithelial cells by transfection accelerated progressi
on to the malignant phenotype. In contrast to the FGFR2 kinase fused t
o the ectodomain of FGFR1, the FGFR1 kinase failed initially to suppor
t a mitogenic response to FGF-2 in type I tumor cells. However, the FG
PR1-transfected cells acquired a mitogenic response after extensive pr
oliferation of the cell population, Resident FGFR2 and ectopic FGFR1 a
ppeared to be partitioned in the type I cells, because neither full-le
ngth nor truncated isoforms of FGFR1 affected the mitogenic response o
f the other, Restoration of the FGFR2IIIb kinase to malignant cells ex
pressing FGFR1 depressed tumor growth rates, restored responsiveness t
o stromal cells, and restored epithelial cell differentiation. These o
bservations reveal that homologous FGFR1 and FGFR2 kinases play very d
ifferent roles in cell growth and differentiation and in development a
nd support of the malignant phenotype.