Gw. Krystal et al., AUTOCRINE GROWTH OF SMALL-CELL LUNG-CANCER MEDIATED BY COEXPRESSION OF C-KIT AND STEM-CELL FACTOR, Cancer research, 56(2), 1996, pp. 370-376
At least 70% of small cell lung cancer (SCLC) tumors and tumor-derived
cell lines coexpress the genes for stem cell factor (SCF) and its rec
eptor, the c-kit proto-oncogene. To assess the impact of coexpression
of the growth factor and receptor on SCLC growth, the NCI-H146 SCLC ce
ll line, which expresses only SCF, was transfected with a c-kit expres
sion vector. Kit protein immunoprecipitated from the transfected cells
had a constitutive level of tyrosine phosphorylation, and these cells
grew more vigorously in serum-free medium compared to control-transfe
cted cells, This growth advantage could be blocked by the addition of
the tyrosine kinase inhibitor herbimycin A, Growth of the c-kit-transf
ected cells could be further enhanced by the addition of bombesin or i
nsulin-like growth factor-1, suggesting that the SCF/c-kit autocrine l
oop could function cooperatively with other SCLC autocrine loops, To f
urther investigate the importance of this autocrine loop, a cell line
that naturally coexpresses SCF and c-kit was transfected with a kinase
-defective c-kit gene. Cells transfected with the defective gene showe
d a marked decrease in their ability to grow under growth factor-free
conditions compared to cells transfected with the empty expression vec
tor. Taken together, these studies demonstrate that the coexpression o
f the stem cell factor and c-kit genes is a major contributor to the g
rowth factor independence of SCLC.