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Expression of Granulocyte-Macrophage Colony-Stimulating Factor Receptors in Human Prostate Cancer

Coralia I. Rivas, Juan Carlos Vera, Fernando Delgado-López, Mark L. Heaney, Victor H. Guaiquil, Rong H. Zhang, Howard I. Scher, Ilona I. Concha, Francisco Nualart, Carlos Cordon-Cardo, and David W. Golde

From the Program in Molecular Pharmacology and Therapeutics, Departments of Medicine and Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY; Instituto de Bioquímica, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile; and Departamento de Histología y Embriología, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile.

We studied the expression and function of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor in the human prostate carcinoma cell line LNCaP and looked for its presence in normal and neoplastic human prostatic tissue. The GM-CSF receptor is composed of two subunits, alpha  and beta . While the isolated alpha  subunit binds GM-CSF at low-affinity, the isolated beta  subunit does not bind GM-CSF by itself; but complexes with the alpha  subunit to form a high-affinity receptor. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) showed expression of mRNAs encoding the alpha  and beta  subunits of the GM-CSF receptor in LNCaP cells, and the presence of the alpha  and beta  proteins was confirmed by immunolocalization with anti-alpha and 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 phosphorylation and induced the proliferation of the LNCaP cells. Immunolocalization studies showed low level expression of GM-CSF alpha  and beta  subunits in normal prostate tissue, with substantial expression in benign prostatic hyperplasia and prominent expression 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 antibodies were also reactive with anti-beta subunit antibodies, indicating that they express high-affinity GM-CSF receptors. Our data show that the LNCaP cells express functional GM-CSF receptors and that prostatic carcinomas have prominent GM-CSF receptor expression. These findings imply that both hyperplastic and neoplastic prostatic tissues may be responsive to GM-CSF.

Blood, Vol. 91 No. 3 (February 1), 1998: pp. 1037-1043
© 1998 by The American Society of Hematology.


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