TPA causes divergent responses of Ca²⁺-dependent and Ca²⁺-independent isoforms of PKC in the nuclei of Caco-2 cells

The present studies were undertaken to examine the expression of PKC isoforms within the nucleus of Caco-2 cells, a cell line widely used to investigate intestinal cell growth and differentiation, in order to begin to explore their roles in modulating gene expression. Purified nuclei were, therefore, prepared from Caco-2 cells and found to contain PKC-ζ, but not -α. The phorbol ester, 12-O-tetradecanoyl phorbol 13-acetate (TPA) caused an acute redistribution of PKC-α to the nucleus, but did not change the distribution of PKC-ζ. Chronic treatment with TPA down-regulated total PKC-α, but not -ζ. Moreover, in contrast to acute TPA treatment, after chronic treatment, nuclear PKC-α was no longer detectable, whereas nuclear PKC-ζ was unchanged. These studies demonstrate for the first time the constitutive expression and divergent responses to TPA of the Ca²⁺-dependent and Ca²⁺-independent isoforms of PKC in the nuclei of Caco-2 cells and suggest that these specific isoforms may be involved in modulating gene expression.