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 566bp products, corresponding to SV1 and SV2 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 (Kd=1.81±0.47nM) and maximum binding capacity of 332.7±27.8fmol/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.
Original language | English (US) |
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Pages (from-to) | 1127-1133 |
Number of pages | 7 |
Journal | Peptides |
Volume | 23 |
Issue number | 6 |
DOIs | |
State | Published - 2002 |
Externally published | Yes |
Keywords
- Growth hormone-releasing hormone
- Prostate cancer
- Receptors for growth hormone-releasing hormone
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
- Physiology
- Cellular and Molecular Neuroscience