Correlation of protein kinase A and protein kinase C activities in normal breast tissue

Abstract

Abstract Because of their central role in the transduction of extracelluar signals, protein kinases A (PKA) and C (PKC) are critical enzymes in the control of cellular proliferation and differentiation. We have measured the catalytic activity of PKA (both as ‘basal activity' which represents the endogenous kinase and ‘total activity' which is that expressed on addition of cyclic AMP (cAMP) and represents the total capacity of the system for PKA phosphorylation) and PKC (as total activity and that subdivided according to whether the kinase was stimulated by Ca 2+ or was Ca 2+ -independent) in samples of normal breast tissue from 45 patients undergoing breast surgery. Spearman correlation analysis revealed strong positive correlations between either basal ( r =0.76, P r = 0.53, P = 0.0002) PKA activity and total PKC activity. Both basal and total PKA activity correlated with Ca 2+ -independent and Ca 2+ -dependent components of total PKC activity, although the correlation of total PKA activity with Ca 2+ -independent PKC was weaker than that with Ca 2+ -dependent PKC. Levels of both PKA and PKC activity increased with the amount of parenchymal tissue present in specimens and correlated within subgroups containing different amounts of parenchymal elements. In 28 samples, regulatory subunits of PKA were measured by assessing total cAMP binding proteins present in samples. These correlated with the levels of PKA catalytic activity of specimens and additionally with both Ca 2+ -independent and Ca 2+ -dependent components of total PKC activity. These data suggest that both PKA and PKC signalling pathways are associated with the expression of parenchymal elements in normal breast tissue. Furthermore, the levels of these two kinases may be coordinately linked in normal breast, although the manner of their interaction will require further experimental clarification.