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.
Plonowski
Artur
A
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, 1601 Perdido Street, New Orleans, LA 70112-1262, USA.
Schally
Andrew V
AV
Busto
Rebeca
R
Krupa
Magdalena
M
Varga
Jozsef L
JL
Halmos
Gabor
G
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