The Regulatory Mechanism of Differentiation and Growth by Prostaglandin D2 in Pigment Cells

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Microphthalmia-associated transcription factor (Mitf) is responsible for differentiation of melanocytes. The black-eyed white (Mi-bw) mouse, a recessive Mitf mutant, lacks melanocytes in hair follicles and inner ear due to the impaired expression of Mitf, thereby exhibiting white coat color and deafness. By cDNA microarray analysis between wild type and Mi-bw mouse skin, we have identified lipocalin-type prostaglandin D synthase (L-PGDS) as a new melanocyte marker. L-PGDS exerts various biological actions in part via production of prostaglandin D_2 (PGD_2). Interestingly L-PGDS is expressed in normal human epidermal melanocytes, but not in human melanoma cell lines, as judged by northern blot and RT-PCR analyses. Such unexpected findings prompted us to examine whether L-PGDS is a potential tumor suppressor. Accordingly, we examined the effect of PGD_2 on the cell growth of human melanoma cells, using HMV-II, SK-MEL-28, 624mel, and G361 cell lines. The growth of melanoma cells was significantly repressed by the treatment with PGD_2, but not with each agonist specific for the PGD_2 receptor, DP1 or DP2, suggesting that PGD_2 may repress the growth of melanoma cells through a mechanism independent of the known PGD_2 receptor. Thus, the loss of L-PGDS expression in melanoma cells may be beneficial for their growth. These results suggest that L-PGDS may function as a potential tumor suppressor in human melanoma cells.