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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, and . While the isolated subunit binds GM-CSF
at low-affinity, the isolated subunit does not bind GM-CSF by
itself; but complexes with the subunit to form a high-affinity
receptor. Quantitative reverse transcriptase-polymerase chain reaction
(RT-PCR) showed expression of mRNAs encoding the and subunits
of the GM-CSF receptor in LNCaP cells, and the presence of
the and proteins was confirmed by immunolocalization with
anti- and anti- 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 and 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- subunit antibodies were also
reactive with anti- 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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