C/EBPdelta is a crucial regulator of pro-apoptotic gene expression during mammary gland involution

Muthusamy Thangaraju1, Martina Rudelius, Brian Bierie

  • 1Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201, USA.

Development (Cambridge, England)
|September 30, 2005
PubMed

Insights

CCAAT/enhancer binding protein delta (C/EBPdelta) is essential for mammary gland involution. Its absence delays cell death, disrupts gene regulation, and impairs protease activation, highlighting its role in epithelial cell apoptosis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • Mammary gland involution is a complex process involving programmed cell death.
  • Signal transducer and activator of transcription 3 (STAT3) initiates involution.
  • The role of STAT3 target genes in mediating apoptosis during involution requires further elucidation.

Purpose of the Study:

  • To investigate the role of CCAAT/enhancer binding protein delta (C/EBPdelta) in mammary epithelial cell apoptosis during involution.
  • To determine if C/EBPdelta acts as a mediator between STAT3 and pro-apoptotic gene expression.
  • To analyze the impact of C/EBPdelta deficiency on key genes regulating cell death and involution.

Main Methods:

  • Analysis of gene expression in mouse models and HC11 cells.
  • Investigating the regulation of pro- and anti-apoptotic genes.
  • Assessing the impact on protease activation and involution timing.

Main Results:

  • C/EBPdelta is a crucial mediator of pro-apoptotic gene expression (p53, BAK, IGFBP5, SGP2/clusterin) during involution.
  • Absence of C/EBPdelta delays involution, prevents activation of pro-apoptotic genes, and fails to repress anti-apoptotic genes (BFL1, Cyclin D1).
  • C/EBPdelta alone induces IGFBP5 and SGP2, suppresses Cyclin D1, and cooperates with p53 to promote apoptosis in HC11 cells.

Conclusions:

  • C/EBPdelta acts as a key downstream mediator of STAT3 signaling during mammary gland involution.
  • C/EBPdelta is essential for the timely activation of pro-apoptotic genes and repression of anti-apoptotic genes, facilitating physiological cell death.
  • This study defines C/EBPdelta's critical position in the molecular cascade initiating mammary epithelial cell apoptosis during involution.

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