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

1.角质形成细胞中MC 1-R的表达：MC 1-R不仅在黑素细胞中表达，而且在角质形成细胞中也有表达，其表达与角质形成细胞的分化状态有关.黑色素瘤中MC 1-R表达与转移能力的相关性：利用黑色素瘤细胞与巨噬细胞的杂交瘤，证实MC 1-R的高表达与转移能力相关. UVB下调酪氨酸酶相关蛋白2（TRP 2）的表达，诱导黑色素瘤细胞凋亡. MC-R亚家族在人黑素细胞/黑素瘤细胞中的表达：在黑素瘤细胞中，除MC 4-R外，检测到所有MC-R亚家族（MC 1-R，2-R，3-R，5-R）。在正常人黑素细胞的情况下，MC 1-R和3-R在所有四种黑素细胞株中检测到，5-R在两种株中检测到，2-R和4-R在一种株中检测到。这表明MC-R亚家族在不同黑素细胞中表达不同，而黑素瘤中不存在异质性。5. PKA和PKC在酪氨酸酶激活中的作用：PKCα和β的反义及PKC抑制剂均能增强FSH诱导的酪氨酸酶活性。加入dbcAMP可增加细胞内cAMP水平和酪氨酸酶活性，而PKC抑制剂则抑制酪氨酸酶活性。总之，PKC作为MSH诱导的酪氨酸酶激活的抑制剂，但作为cAMP诱导的酪氨酸酶激活的激活剂。

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.