EXPRESSION OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR RECEPTORS IN HUMAN PROSTATE-CANCER

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.