Impact of NAD(P)H:quinone oxidoreductase-1 on pigmentation.
We obtained metastasized melanoma tissue from a primary acral lentiginous melanoma (ALM) patient and established a melanoma cell line named primary culture of melanoma cell derived from lymph node (PML)-1. PML-1 cells had a light brown color and decreased the expression of melanogenesis markers, including tyrosinase (TYR), microphthalmia-associated transcription factor, and tyrosinase-related protein-1. To identify genes differentially regulated in PML-1 melanoma cells, we performed DNA microarray and two-dimensional matrix-assisted laser desorption ionization-time of flight mass spectrometry analyses. Among the candidate genes identified, we chose NAD(P)H:quinone oxidoreductase-1 (NQO1) for further study. Reverse transcription-PCR and western blot analyses showed that NQO1 was markedly decreased in PML-1 cells and in several amelanotic melanoma cell lines. To investigate whether NQO1 affects the melanogenesis, we treated the cultured normal human melanocytes (NHMC) and zebrafish with NQO1 inhibitors, ES936 and dicoumarol. Interestingly, melanogenesis was significantly decreased by the addition of NQO1 inhibitors in both NHMC and zebrafish models. In contrast, overexpression of NQO1 using a recombinant adenovirus clearly induced melanogenesis, concomitantly with an increase of TYR protein level. These results suggest that NQO1 is a positive regulator of the pigmentation process.
Choi
Tae-Young
TY
Department of Dermatology, School of Medicine, Research Institute for Medical Sciences, Chungnam National University, Daejeon, Korea.
Sohn
Kyung-Cheol
KC
Kim
Jin-Hwa
JH
Kim
Seong-Min
SM
Kim
Cheol-Hee
CH
Hwang
Jae-Sung
JS
Lee
Jeung-Hoon
JH
Kim
Chang Deok
CD
Yoon
Tae-Jin
TJ
D000256:Adenoviridae / Q000235:genetics; D000470:Alkaloids / Q000096:biosynthesis; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008198:Lymph Nodes / Q000166:cytology; D008543:Melanins / Q000096:biosynthesis; D008544:Melanocytes / Q000166:cytology / Q000502:physiology; D008545:Melanoma / Q000378:metabolism / Q000503:physiopathology; D014442:Monophenol Monooxygenase / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism / Q000503:physiopathology; D012880:Skin Pigmentation / Q000235:genetics*; D015027:Zebrafish
D000470:Alkaloids; D014408:Biomarkers, Tumor; D008543:Melanins; D011994:Recombinant Proteins; C039649:melinonine F; D014442:Monophenol Monooxygenase; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human