Substantial expression of luteinizing hormone-releasing hormone (LHRH) receptor type I in human uveal melanoma
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Andrea Treszl1,*, Zita Steiber2,*, Andrew V. Schally3,4 , Norman L Block3,4 , Balazs Dezso5, Gabor Olah1, Bernadett Rozsa1, Klara Fodor1, Armin Buglyo1, Janos Gardi6, Andras Berta2 and Gabor Halmos1,3
1 Department of Biopharmacy, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary
2 Department of Ophthalmology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary
3 Veterans Affairs Medical Center Miami, FL, South Florida VA Foundation for Research and Education, Miami, FL and Department of Pathology, University of Miami, Miller School of Medicine, Miami, FL, USA
4 Divisions of Hematology/Oncology and Endocrinology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL, USA
5 Department of Pathology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary
6 Department of Endocrinology, University of Szeged, Faculty of Medicine, Szeged, Hungary
* These authors contributed equally to this work.
Gabor Halmos, email:
Andrew V. Schally, email:
Keywords: uveal melanoma, luteinizing hormone-releasing hormone (LHRH) receptor
Received: September 5, 2013 Accepted: September 8, 2013 Published: September 10, 2013
Uveal melanoma is the most common primary intraocular malignancy in adults, with a very high mortality rate due to frequent liver metastases. Consequently, the therapy of uveal melanoma remains a major clinical challenge and new treatment approaches are needed. For improving diagnosis and designing a rational and effective therapy, it is essential to elucidate molecular characteristics of this malignancy. The aim of this study therefore was to evaluate as a potential therapeutic target the expression of luteinizing hormone-releasing hormone (LHRH) receptor in human uveal melanoma. The expression of LHRH ligand and LHRH receptor transcript forms was studied in 39 human uveal melanoma specimens by RT-PCR using gene specific primers. The binding charachteristics of receptors for LHRH on 10 samples were determined by ligand competition assays. The presence of LHRH receptor protein was further evaluated by immunohistochemistry. The expression of mRNA for type I LHRH receptor was detected in 18 of 39 (46%) of tissue specimens. mRNA for LHRH-I ligand could be detected in 27 of 39 (69%) of the samples. Seven of 10 samples investigated showed high affinity LHRH-I receptors. The specific presence of full length LHRH receptor protein was further confirmed by immunohistochemistry. A high percentage of uveal melanomas express mRNA and protein for type-I LHRH receptors. Our results support the merit of further investigation of LHRH receptors in human ophthalmological tumors. Since diverse analogs of LHRH are in clinical trials or are already used for the treatment of various cancers, theseanalogs could be considered for the LHRH receptor-based treatment of uveal melanoma.
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