Expression of proliferating cell nuclear antigen (PCNA): proliferative phase functions and malignant transformation of melanocytes.

The UV-dependent G2-phase functions of melanocytes include dendricity, the expression of melanocyte stimulating hormone (MSH) receptors and neural differentiation. The present report studied highly dendritic melanocytes in epidermis overlying tumours, seborrhoeic keratosis, basal cell carcinoma and melanomas. The expression of the proliferative protein PCNA was studied by immunohistochemistry, as this indicates cells in S/G2-phase. In the non-neoplastic dendritic melanocytes, PCNA is retained in the cytoplasm, resulting in the arrest of the cells in the S/G2-phase for prolonged periods, as indicated by the length and complexity of the dendritic processes. In melanomas, this barrier is overcome with rapid proliferation of the cells and loss of dendricity. PCNA is produced in the cytoplasm and transported into the nucleus during the S-phase, as observed in melanomas. The arrest of melanocytes in the S/G2-phase for long periods associated with UV responsiveness makes these cells vulnerable to DNA damage and neoplasia. Pools of PCNA in the cytoplasm, when transported into the nucleus, would support the rapid proliferation observed in melanomas.