Local signals induce CCAAT/enhancer binding protein-delta (C/EBP-delta) and C/EBP-beta mRNA expression in the involuting mouse mammary gland.
The repeated lactation cycles in the mammary gland offer a unique environment for the study of cell growth, differentiation, and death. The CCAAT/enhancer binding proteins (C/EBPs) are a family of transcription factors important in growth control and differentiation in many tissues. Our laboratory and others have shown that C/EBP-delta and C/EBP-beta mRNA expression is closely associated with normal mouse mammary gland involution. To examine the relative influence of local versus systemic factors in C/EBP expression and tissue remodeling, a gland sealing mouse model was used. Mice with unilateral sealing continue to lactate and nurse pups via nonsealed glands, while sealed glands initiate involution. The expression of C/EBP-alpha, beta and delta mRNA was investigated in sealed and nonsealed nursing glands. In situ apoptosis was documented and glandular morphology was also examined. C/EBP-delta mRNA levels are low in nonsealed glands, but are rapidly and transiently induced in sealed glands by 24 h. C/EBP-beta mRNA expression is also relatively low in nonsealed glands, but is induced in sealed glands within 72 h. Expression of the apoptosis-associated mRNAs encoding bax and TRPM-2 is also induced in sealed glands by 24-48 h. Apoptosis and a moderate degree of tissue remodeling occur within the sealed glands in spite of systemic hormone levels capable of sustaining lactation. These data demonstrate that local factors are sufficient to induce C/EBP-beta and C/EBP-delta in the mouse mammary gland. In addition, mammary epithelial apoptosis and glandular remodeling occur in sealed glands, confirming a critical role for local factors in mammary involution.
Gigliotti
A P
AP
The Ohio State University, Department of Veterinary Biosciences, Columbus 43210, USA.
DeWille
J W
JW
D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D020287:In Situ Nick-End Labeling; D007774:Lactation / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors