We studied the expression and function of the granulocyte-macrophage c
olony-stimulating factor (GM-CSF) receptor in the human prostate carci
noma cell line LNCaP and looked for its presence in normal and neoplas
tic human prostatic tissue. The GM-CSF receptor is composed of two sub
units, alpha and beta. While the isolated alpha subunit binds GM-CSF a
t low-affinity, the isolated beta subunit does not bind GM-CSF by itse
lf; but complexes with the alpha subunit to form a high-affinity recep
tor. Quantitative reverse transcriptase-polymerase chain reaction (RT-
PCR) showed expression of mRNAs encoding the alpha and beta subunits o
f the GM-CSF receptor in LNCaP cells, and the presence of the alpha an
d beta proteins was confirmed by immunolocalization with anti-alpha an
d anti-beta antibodies. Receptor binding studies using radiolabeled GM
-CSF showed that LNCaP cells have about 150 high-affinity sites with a
kd of 40 pmol/L and approximately 750 low-affinity sites with a kd of
2 nmol/L. GM-CSF signaled, in a time- and dose-dependent manner. for
protein tyrosine phoshorylation and induced the proliferation of the L
NCaP cells. Immunolocalization studies showed low level expression of
GM-CSF alpha and beta subunits in normal prostate tissue, with substan
tial expression in benign prostatic hyperplasia and prominent expressi
on in neoplastic prostate tissue, Maximal expression of both subunits
was observed in prostatic carcinomas metastatic to lymph node and bone
. Tumor cells that stained positively with anti-alpha subunit antibodi
es were also reactive with anti-beta subunit antibodies, indicating th
at they express high-affinity GM-CSF receptors. Our data show that the
LNCaP cells express functional GM-CSF receptors and that prostatic ca
rcinomas have prominent GM-CSF receptor expression. These findings imp
ly that both hyperplastic and neoplastic prostatic tissues may be resp
onsive to GM-CSF. (C) 1998 by The American Society of Hematology.