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001-es BibID:BIBFORM071428
Első szerző:Sipos Éva (gyógyszerész)
Cím:Characterization of Luteinizing hormone-releasing hormone (LH-RH-I) receptor type I as a potential molecular target in OCM-1 and OCM-3 human uveal melanoma cell lines / Eva Sipos, Nikoletta Dobos, David Rozsa, Klara Fodor, Gabor Olah, Zsuzsanna Szabo, Lorant Szekvolgyi, Andrew V. Schally, Gabor Halmos
Dátum:2018
Megjegyzések:Uveal melanoma (UM) is the most common primary intraocular malignancy with very poor prognosis. Conventional chemotherapy only rarely prolongs the survival, therefore patients require novel treatment modalities. The discovery of specific receptors for hypothalamic hormones on cancer cells has led to the development of radiolabeled and cytotoxic hormone analogs.In the present study, our aim was to investigate the expression of mRNA for receptors of luteinizing hormone-releasing hormone type I (LH-RH-I) and LH-RH ligand in OCM-1 and OCM-3 human uveal melanoma cell lines. The presence and binding characteristics of LH-RH-I receptor protein was further studied by Western blot, immunocytochemistry and ligand competition assay. The expression of mRNA and protein for LH-RH-I receptors has been also studied using tumor samples originating from nude mice xenografted with OCM-1 or OCM-3 cells.The mRNA for LH-RH-I receptor has been detected in OCM-1 and OCM-3 cell lines and wasfound markedly higher in OCM-3 cells. The mRNA for LH-RH-I receptors was also observed in both UM xenograft models in vivo with higher levels in OCM-3. The presence of LH-RH-I receptor protein was found in both cell lines in vitro by immunocytochemistry and Western blot, and also in tumor tissue samples grown in nude mice by Western blot. Both human uveal melanoma models investigated showed specific high affinity receptors for LH-RH-I using ligand competition assay. The mRNA for LH-RH ligand has also been detected in OCM-1 and OCM-3 cell lines and cancer tissues.In summary, the demonstration of the expression of LH-RH-I receptors in OCM-1 and OCM-3 human UM cell lines suggests that they could serve as potential molecular target for therapy. Our findings support the development of new therapeutic approaches based on cytotoxic LH-RH analogs or modern powerful antagonistic analogs of LH-RH targeting LH-RH-I receptors in UM.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
human uveal melanoma
luteinizing hormone-releasing hormone receptor
luteinizing hormone-releasing hormone ligand
targeted cancer therapy
cancer
luteinizing hormone-releasing hormone
Megjelenés:Oncotargets and Therapy. - 11 (2018), p. 933-941. -
További szerzők:Dobos Nikoletta (1981-) (biológus) Rózsa Dávid (1982-) (Ph.D hallgató) Molnár-Fodor Klára (1989-) (biotechnológus) Oláh Gábor (1987-) (gyógyszerész) Szabó Zsuzsanna Székvölgyi Lóránt (1977-) (biofizikus, biokémikus, sejtbiológus) Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Pályázati támogatás:K81596
OTKA
4.2.2.A-11/1KONV-2012-0025
TÁMOP
TÁMOP-4.2.2/B-10/1-2010-0024
TÁMOP
Gyógyszerészeti Tudományok Doktori Iskola
GINOP-2.3.2-15-2016-00043
GINOP
MTA-DE Lendület Genomszerkezet és Rekombináció kutatócsoport
MTA
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
DOI
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