Abstract |
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.
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Authors | Artur Plonowski, Andrew V Schally, Rebeca Busto, Magdalena Krupa, Jozsef L Varga, Gabor Halmos |
Journal | Peptides
(Peptides)
Vol. 23
Issue 6
Pg. 1127-33
(Jun 2002)
ISSN: 0196-9781 [Print] United States |
PMID | 12126741
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Peptides
- Protein Isoforms
- RNA, Messenger
- Receptors, Neuropeptide
- Receptors, Pituitary Hormone-Regulating Hormone
- Growth Hormone-Releasing Hormone
- somatotropin releasing hormone receptor
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Topics |
- Alternative Splicing
- Animals
- Cell Division
- Dose-Response Relationship, Drug
- Growth Hormone-Releasing Hormone
(biosynthesis, chemistry)
- Humans
- Kinetics
- Male
- Mice
- Mice, Nude
- Neoplasm Transplantation
- Neoplasms, Experimental
- Peptides
(chemistry)
- Polymerase Chain Reaction
- Prostatic Neoplasms
(metabolism)
- Protein Isoforms
- RNA, Messenger
(metabolism)
- Radioligand Assay
- Receptors, Neuropeptide
(biosynthesis, chemistry)
- Receptors, Pituitary Hormone-Regulating Hormone
(biosynthesis, chemistry)
- Reverse Transcriptase Polymerase Chain Reaction
- Tumor Cells, Cultured
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