Protein kinase A and AP-1 (c-Fos/JunD) are induced during apoptosis of mouse mammary epithelial cells

Abstract

At weaning the mammary gland undergoes a reductive remodelling process (involution) which is associated with the cessation of milk protein gene expression and programmed cell death of milk-producing epithelial cells. Elevated nuclear protein kinase A (PKA) activity was observed from 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 was transiently induced and the AP-1 complex was shown to consist principally 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, whereas 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 that PKA activation, AP-1 induction and Oct-1 inactivation all are dependent on the presence of the epithelial compartment. The increased Fos/Jun expression and the inactivation of Oct-1 may be consequences of the increased PKA activity. A similar induction of AP-1 (cFos/JunD) was also observed in the involuting rat ventral prostate pointing to a possible role for AP-1 in programmed cell death.