Substantial expression of luteinizing hormone-releasing hormone (LHRH) receptor type I in human uveal melanoma.
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.
Department of Biopharmacy, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary.
Andrea
A
Treszl
Zita
Z
Steiber
Andrew V
AV
Schally
Norman L
NL
Block
Balazs
B
Dezso
Gabor
G
Olah
Bernadett
B
Rozsa
Klara
K
Fodor
Armin
A
Buglyo
Janos
J
Gardi
Andras
A
Berta
Gabor
G
Halmos
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011966:Receptors, LHRH / Q000096:biosynthesis* / Q000235:genetics; D014604:Uveal Neoplasms / Q000235:genetics / Q000378:metabolism*; D000098943:Uveal Melanoma
D012333:RNA, Messenger; D011966:Receptors, LHRH