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 |
|---|---|
| Pages (from-to) | 1127-1133 |
| Number of pages | 7 |
| Journal | Peptides |
| Volume | 23 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jul 30 2002 |
| Externally published | Yes |
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Keywords
- Growth hormone-releasing hormone
- Prostate cancer
- Receptors for growth hormone-releasing hormone
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
- Physiology
- Cellular and Molecular Neuroscience
Cite this
Expression of growth hormone-releasing hormone (GHRH) and splice variants of GHRH receptors in human experimental prostate cancers. / Plonowski, Artur; Schally, Andrew V; Busto, Rebeca; Krupa, Magdalena; Varga, Jozsef L.; Halmos, Gabor.
In: Peptides, Vol. 23, No. 6, 30.07.2002, p. 1127-1133.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Expression of growth hormone-releasing hormone (GHRH) and splice variants of GHRH receptors in human experimental prostate cancers
AU - Plonowski, Artur
AU - Schally, Andrew V
AU - Busto, Rebeca
AU - Krupa, Magdalena
AU - Varga, Jozsef L.
AU - Halmos, Gabor
PY - 2002/7/30
Y1 - 2002/7/30
N2 - 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.
AB - 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.
KW - Growth hormone-releasing hormone
KW - Prostate cancer
KW - Receptors for growth hormone-releasing hormone
UR - http://www.scopus.com/inward/record.url?scp=0035996854&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035996854&partnerID=8YFLogxK
U2 - 10.1016/S0196-9781(02)00043-8
DO - 10.1016/S0196-9781(02)00043-8
M3 - Article
C2 - 12126741
AN - SCOPUS:0035996854
VL - 23
SP - 1127
EP - 1133
JO - Peptides
JF - Peptides
SN - 0196-9781
IS - 6
ER -