Mechanism of Hormonal Regulation of CAD Gene Expression in Human Breast Cancer Cells

Abstract

The cad gene is trifunctional and expresses carbamoylphosphate synthetase/aspartate carbamyltransferase/dihydroorotase, which are required for pyrimidine biosynthesis. Treatment of ZR-75 cells with 10 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in significant downregulation of E2-induced cad mRNA levels. The mechanism of TCDD-induced downregulation was further investigated using constructs containing the growth-responsive -90 to +115 (pCAD1) and -90 to +115 (pCAD2) region of the cad gene promoter. E2 induced reporter gene (luciferase) activity in MCF-7 and ZR-75 cells transfected with pCAD1 and pCAD2 and this transactivation was inhibited by TCDD. Moreover proteosome inhibitor MG132 did not reverse the effects of TCDD on cad gene expression suggesting that limiting levels of ER may not be the factor in the observed downregulation by TCDD. Also treatment of ZR75 cells with PPAR gamma agonist PGJ2 resulted in downregulation of E2-induced cad gene expression suggesting a possible crosstalk between ER and PPAR gamma signaling pathways.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2004
Accession Number
ADA429488

Entities

People

  • Shaheen Khan

Organizations

  • Texas A&M University

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Anabolism
  • Antineoplastic Agents
  • Biomedical Research
  • Breast Cancer
  • Cell Line
  • Cells
  • Co-Channel Interference
  • Estrogens
  • Gene Expression
  • Inhibition
  • Inhibitors
  • Metabolism
  • Neoplasms
  • Regulations
  • Tissue Extracts
  • Tumor Cell Line

Readers

  • Breast cancer cell signaling and growth regulation.
  • Oncology and Biomarker-Based Cancer Detection.