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 i soforms within the nucleus of Caco-2 cells, a cell line widely used to investigate intestinal cell growth and differentiation, in order to b egin to explore their roles in modulating gene expression. Purified nu clei were, therefore, prepared from Caco-2 cells and found to contain PKC-zeta, but not -alpha. The phorbol ester, 12-O-tetradecanoyl phorbo l 13-acetate (TPA) caused an acute redistribution of PKC-alpha to the nucleus, but did not change the distribution of PKC-zeta. Chronic trea tment with TPA down-regulated total PKC-alpha, but not -zeta. Moreover , in contrast to acute TPA treatment, after chronic treatment, nuclear PKC-alpha was no longer detectable, whereas nuclear PKC-zeta was unch anged. These studies demonstrate for the first time the constitutive e xpression and divergent responses to TPA of the Ca2+-dependent and Ca2 +-independent isoforms of PKC in the nuclei of Caco-2 cells and sugges t that these specific isoforms may be involved in modulating gene expr ession.