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001-es BibID:BIBFORM033602
035-os BibID:PMID:12364462 WOS:000178649800050
Első szerző:Halmos Gábor (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Cím:Expression of growth hormone-releasing hormone and its receptor splice variants in human prostate cancer / Gabor Halmos, Andrew V. Schally, Tamas Czompoly, Magdalena Krupa, Jozsef L. Varga, Zoltan Rekasi
Dátum:2002
ISSN:0021-972X
Megjegyzések:Antagonists of GHRH inhibit the growth of various human tumors, including prostate cancer, but the tumoral receptors mediating the antiproliferative effect of GHRH antagonists have not been clearly identified. Recently, we demonstrated that human cancer cell lines express splice variants (SVs) of receptors for GHRH, of which SV1 exhibits the greatest similarity to the pituitary GHRH receptors. In this study we investigated the expression of GHRH and SVs of GHRH receptor and the binding characteristics of the GHRH receptor isoform in 20 surgical specimens of organ-confined and locally advanced human prostatic adenocarcinomas. The mRNA expression of GHRH and SVs of GHRH receptor was investigated by RT-PCR. The affinity and density of receptors for GHRH were determined by ligand competition assays based on binding of (125)I-labeled GHRH antagonist JV-1-42 to tumor membranes. Twelve of 20 tumors (60%) exhibited specific, high affinity binding for JV-1-42, with a mean dissociation constant (K(d)) of 0.81 nmol/liter and a mean maximal binding capacity of 185.2 fmol/mg membrane protein. The mRNA of SV1 was detected in 13 of 20 (65%) prostate cancer specimens and was consistent with the presence of GHRH binding. RT-PCR analyses also revealed the expression of mRNA for GHRH in 13 of 15 (86%) prostatic carcinoma specimens examined. The presence of GHRH and its tumoral receptor SVs in prostate cancers suggests the possible existence of an autocrine mitogenic loop. The antitumor effects of GHRH antagonists in prostate cancer could be exerted in part by interference with this local GHRH system.
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Megjelenés:Journal of Clinical Endocrinology & Metabolism. - 87 : 10 (2002), p. 4707-4714. -
További szerzők:Schally, Andrew Victor Czompoly Tamás Krupa, Magdalena Varga József L. Rékási Zoltán
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