PROTEIN KINASE-A AND AP-1 (C-FOS JUND) ARE INDUCED DURING APOPTOSIS OF MOUSE MAMMARY EPITHELIAL-CELLS/

At weaning the mammary gland undergoes a reductive remodelling process (involution) which is associated with the cessation of milk protein g ene expression and programmed cell death of milk-producing epithelial cells. Elevated nuclear protein kinase A (PKA) activity was observed f rom one day post-lactation, paralleled by increased c-fos, junB, junD and to a lesser extent c-jun mRNA levels. AP-1 DNA binding activity wa s transiently induced and the AP-1 complex was shown to consist princi pally of cFos/JunD. Oct-1 DNA binding activity and Oct-1 protein were gradually lost from the gland over the first 4 days of involution, whe reas Oct-1 mRNA levels remained unchanged. Comparing nuclear extracts from normal mammary glands with nuclear extracts from glands which had been cleared of all epithelial cells 3 weeks after birth, revealed th at PKA activation, AP-1 induction and Oct-1 inactivation all are depen dent on the presence of the epithelial compartment. The increased Fos/ Jun expression and the inactivation of Oct-1 may be consequences of th e increased PKA activity. A similar induction of AP-1 (cFos/JunD) was also observed in the involuting rat ventral prostate pointing to a pos sible role for AP-1 in programmed cell death.