Enhanced Melanogenesis Induced by Tyrosinase Gene-Transfer Increases Boron-Uptake and Killing Effect of Boron Neutron Capture Therapy for Amelanotic Melanoma
| Autor: | Hirofumi Kondoh, Tatsuya Tsuboi, Yutaka Mishima, Junichi Hiratsuka |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Boron Compounds
Indoles Phenylalanine Tyrosinase Clinical Biochemistry Gene Expression chemistry.chemical_element Boron Neutron Capture Therapy Plant Science Photochemistry Melanin Mice Gene expression medicine Animals Indolequinones Amelanotic melanoma Boron Cells Cultured Melanins Monophenol Monooxygenase Reverse Transcriptase Polymerase Chain Reaction Chemistry Melanoma Gene Transfer Techniques Quinones Cancer Melanoma Amelanotic Cell Biology medicine.disease Kinetics Cell culture Cancer research Agronomy and Crop Science Developmental Biology |
| Zdroj: | Pigment Cell Research. 11:275-282 |
| ISSN: | 1600-0749 0893-5785 |
| DOI: | 10.1111/j.1600-0749.1998.tb00736.x |
| Popis: | Specific and powerful cancer killing effect for melanoma by boron neutron capture therapy (BNCT) using DOPA analogue, 10B-p-boronophenylalanine (10B-BPA), has been established, but amelanotic melanoma is insufficiently responsive to 10B-BPA BNCT in comparison with actively melanin-producing melanoma. Although the accumulation mechanism of 10B-BPA within melanoma was not established, we have recently obtained findings suggesting that melanin monomers, key intermediates for melanin polymer formation, play a critical role in 10B-BPA accumulation. In addition, there are some kinds of human amelanotic melanomas, such as MEL2A, in which expression of tyrosinase is repressed or lacking though tyrosinase-related protein (TRP)-1 and TRP-2 are well expressed. Thus, by using a similarly tyrosinase-lacking mouse amelanotic melanoma cell line, A1059, we constructed TA1059 cells by transfecting human tyrosinase-cDNA into these cells. TA1059 cells acquired higher DOPA-oxidase and DOPAchrome tautomerase activity as well as eumelanin content at even higher levels than those of B16F10 cells. TA1059 cells showed about 2.5 times higher P-boronophenylalanine (BPA) uptake than A1059 cells in culture. In animal experiments, by using these cell lines, tumor growth of TA1059 was significantly suppressed by 10B-BPA BNCT as compared with A1059. These findings indicate that the induction of active melanin biosynthesis by melanogenic gene-transfer effectively improves the treatment of amelanotic melanoma by BNCT. |
| Databáze: | OpenAIRE |
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