ELEVATION OF PROTEIN-KINASE-A AND PROTEIN-KINASE-C ACTIVITIES IN MALIGNANT AS COMPARED WITH NORMAL HUMAN BREAST-TISSUE

Because of their central role in the transduction of extracellular sig nals, protein kinases A (PKA) and C (PKC) are critical enzymes in the control of cellular proliferation and differentiation, We have measure d the catalytic activity of PKA and PKC, as well as the regulatory sub unit expression for PKA, in paired samples of normal and malignant bre ast tissue from 13 patients with breast cancer. Paired non-parametric (Wilcoxon) analysis revealed significantly higher values for both basa l (P = 0.0002) and total (P = 0.0002) PKA catalytic activity in malign ant compared with normal breast in all 13 paired tissue samples. Expre ssion of both R(I)- and R(II)-PKA regulatory subunits were also higher in malignant tissue from 12 (P = 0.0005) and 9 (P = 0.01) of the 13 p airs, respectively. However, the degree of R(I)-subunit overexpression in malignant tissue was greater than that of the R(II)-subunit, as de monstrated by an increase in the R(I)/R(II) subunit ratio in 10 of the 13 paired samples (P = 0.017). Total PKC catalytic activity was eleva ted in 11 of the 13 malignant tissue specimens when compared with corr esponding normal breast tissue (P = 0.01). This was accounted for by a n increase in Ca2+-dependent PKC activity (P = 0.01), there being no s ignificant increase in Ca2+-independent PKC activity. These data sugge st that the activities of both PKA and PKC signalling pathways are int rinsically higher in malignant compared with normal breast tissue and these may therefore represent targets for interventive treatment of br east cancer. Copyright (C) 1996 Elsevier Science Ltd