Analysis of the role of the expression of MSH receptor subspecies in growth, differentiation, and metastasis in pigment cells

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1. MC1-R expression in keratinocytes : MC1-R was expressed in not only melanocytes but also keratinocytes and their expression was correlated with their differentiation state.2. Correlation of MC1-R expression and metastatic ability in melanomas : Using the hybridoma of melanoma cells and macrophage, higher expression of MC1-R was proved to be correlated with metastatic ability.3. Downregulation of the expression of tyrosinase related protein 2 (TRP2) by UVB induced apoptotic change of melanoma cells.4. Expression of MC-R subfamily in human melanocytes/melanoma cells : In melanoma cells, all MC-R subfamilies (MC1-R, 2-R, 3-R, 5-R) except MC4-R was detected. In case of normal human melanocytes, MC1-R and 3-R was detected in all four strains of melanocytes, 5-R in two strains, 2-R and 4-R in one strain. This indicates that MC-R subfamily is differently expressed among different melanocytes, in contrast there is no heterogeneity in melanomas.5. The role of PKA and PKC in the activation of tyrosinase : The antisense of PKCα and β, and inhibitor of PKC enhanced MSH-induced tyrosinase activity. The addition of dbcAMP increased intracellular level of cAMP and tyrosinase activity, but inhibitior of PKC suppressed tyrosinase activity. Taken together, PKC acts as an inhibitor of MSH-induced activation of tyrosinase but as an activator of cAMP-induced activation of tyrosinase.