Expression of growth hormone-releasing hormone (GHRH) and splice variants of GHRH receptors in human experimental prostate cancers.
The expression of mRNA for GHRH and splice variants (SVs) of GHRH receptors in LNCaP, MDA-PCa-2b and PC-3 human prostate cancers grown in nude mice was investigated by RT-PCR. The expression of mRNA for GHRH was detected in LNCaP and PC-3, but not in MDA-PCa-2b prostatic carcinoma. RT-PCR analyses of mRNA isolated from LNCaP, MDA-PCa-2b and PC-3 cancers, revealed the presence of 720 and 566 bp products, corresponding to SV(1) and SV(2) isoforms of GHRH receptors. In PC-3 tumor membranes a radiolabeled GHRH antagonist [125I]-JV-1-42 was bound to one class of high-affinity binding sites (K(d)=1.81+/-0.47 nM) and maximum binding capacity of 332.7+/-27.8 fmol/mg membrane protein. The in vivo uptake of [125I]-JV-1-42 was observed in all xenografts of human prostate cancer, the tracer accumulation being the highest in PC-3 tumors. These results indicate that GHRH and SVs of its receptors, different from those found in the pituitary, are present in experimental human prostate cancers and may form a local mitogenic loop. The antiproliferative effects of GHRH antagonists on growth of prostate cancer could be exerted in part by an interference with this local GHRH system.
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, 1601 Perdido Street, New Orleans, LA 70112-1262, USA.
Artur
A
Plonowski
Andrew V
AV
Schally
Rebeca
R
Busto
Magdalena
M
Krupa
Jozsef L
JL
Varga
Gabor
G
Halmos
D017398:Alternative Splicing; D000818:Animals; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D013007:Growth Hormone-Releasing Hormone / Q000096:biosynthesis* / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental; D010455:Peptides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000378:metabolism*; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D011869:Radioligand Assay; D018013:Receptors, Neuropeptide / Q000096:biosynthesis* / Q000737:chemistry; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000096:biosynthesis* / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D010455:Peptides; D020033:Protein Isoforms; D012333:RNA, Messenger; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D013007:Growth Hormone-Releasing Hormone; C048250:somatotropin releasing hormone receptor