Apoptotic cell death and tissue remodelling during mouse mammary gland involution
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1Laboratory for Clinical and Experimental Research, University of Bern, Switzerland.
Abstract:
During post-lactational mammary gland involution, the bulk of mammary epithelium dies and is reabsorbed. This massive cell death and tissue restructuring was found to be accompanied by a specific pattern of gene expression. Northern blot analysis showed that weaning resulted in a dramatic drop in ODC, a gene involved in synthesis of a component of milk, and the nearly simultaneous induction of SGP-2, a gene associated with apoptotic cell death. These changes were followed by decreases in expression of milk protein genes to basal levels and expression of genes associated with regulation of cell proliferation and differentiation, p53, c-myc and TGF-beta 1. Subsequently, additional genes implicated in stress response, tissue remodelling, and apoptotic cell death were transiently expressed, expression peaking at about 6 days post-weaning. A non-random degradation of DNA yielding the oligonucleosomal length fragmentation pattern typical of apoptotic cell death (Wyllie, 1980; Wyllie et al., 1980) was detected in association with morphological changes and gene expression. The correlations between: (a) changes in morphology, (b) pattern of gene expression and (c) changes in DNA integrity suggest that complementary programs for cell death and tissue remodelling direct post-lactational mammary gland involution.
Insights
Post-lactational mammary gland involution involves programmed cell death and tissue remodeling. Gene expression patterns, including ornithine decarboxylase (ODC) and SGP-2, correlate with morphological changes and DNA fragmentation during this process.
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Biology
Background:
- Post-lactational mammary gland involution is a complex process involving significant tissue restructuring.
- This involution is characterized by massive epithelial cell death and reabsorption.
Purpose of the Study:
- To investigate the specific gene expression patterns accompanying mammary gland involution.
- To correlate gene expression changes with morphological alterations and DNA integrity during involution.
Main Methods:
- Northern blot analysis was used to examine gene expression levels.
- Morphological changes and DNA fragmentation patterns indicative of apoptosis were assessed.
Main Results:
- Weaning led to a sharp decrease in ornithine decarboxylase (ODC) and induction of SGP-2, a gene linked to apoptosis.
- Expression of milk protein genes, p53, c-myc, and TGF-beta 1 decreased, while genes for stress response and tissue remodeling were transiently upregulated.
- Oligonucleosomal DNA fragmentation, characteristic of apoptosis, was observed alongside morphological changes and altered gene expression.
Conclusions:
- Complementary programs of cell death and tissue remodeling orchestrate post-lactational mammary gland involution.
- The observed correlations between morphology, gene expression, and DNA integrity support a programmed mechanism for involution.