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 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.
Marti
A
A
Laboratory for Clinical and Experimental Research, University of Bern, Switzerland.
Jehn
B
B
Costello
E
E
Keon
N
N
Ke
G
G
Martin
F
F
Jaggi
R
R
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002364:Caseins / Q000235:genetics; D017868:Cyclic AMP-Dependent Protein Kinases / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000235:genetics; D015536:Down-Regulation; D005786:Gene Expression Regulation; D051863:Host Cell Factor C1; D007774:Lactation; D008297:Male; D008321:Mammary Glands, Animal / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008894:Milk Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D050811:Octamer Transcription Factor-1; D011467:Prostate / Q000378:metabolism; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000235:genetics; D014886:Weaning; D000067816:Whey Proteins
D002364:Caseins; D004268:DNA-Binding Proteins; C497693:Hcfc1 protein, mouse; D051863:Host Cell Factor C1; D008894:Milk Proteins; D050811:Octamer Transcription Factor-1; C494166:Pou2f1 protein, mouse; C494168:Pou2f1 protein, rat; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D000067816:Whey Proteins; D017868:Cyclic AMP-Dependent Protein Kinases