Expression of the c-kit tyrosine kinase growth factor receptor has bee
n reported in some breast tumors; however, no data exist concerning ex
pression of its ligand, stem cell factor. The aim of this study was to
determine how frequently the c-kif and stem cell factor genes were co
expressed in breast tumors and tumor-derived cell lines and to determi
ne whether coexpression of c-kif and stem cell factor could result in
growth stimulation of breast tumor cells. Expression of the c-kif and
stem cell factor genes in tissue specimens and cell lines was determin
ed using an RNase protection assay, with confirmation of c-kit protein
expression by immunohistochemistry and Western blotting in tumor tiss
ue and cell lines, respectively. Of 11 tumor specimens studied, 9 expr
essed variable but detectable quantities of c-kif; 7 of 13 tumor-deriv
ed cell lines also expressed c-kif. All tumor specimens and cell lines
expressed detectable stem cell factor mRNA, suggesting that an autocr
ine growth loop could exist in the majority of breast carcinomas. To d
etermine the biological effects of coexpression of c-kif and stem cell
factor, the MCF-7 cell line, which expresses only stem cell factor, w
as transfected with a c-kif expression vector. Coexpression of c-kit a
nd stem cell factor in MCF-7 cells resulted in an enhanced growth rate
and cloning efficiency but not a loss of the dependence of this cell
line upon estrogen. Analysis of subclones expressing different amounts
of c-kit protein revealed that, although they all showed enhanced gro
wth relative to control transfectants in serum-free medium containing
IGF-1, only the highest c-kit expressor responded with additional grow
th to exogenous soluble stem cell factor. However, all c-kit-expressin
g clones, but not control clones, showed growth inhibition when expose
d to a blocking anti-c-kif antibody. This blocking antibody also signi
ficantly inhibited the growth of the established ZR75-1 cell line in s
erum-free medium containing IGF-1. Taken together, these data suggest
that coexpression of stem cell factor and c-kif could be responsible f
or growth deregulation in a significant number of breast carcinomas.