Involvement of Steroid Receptor Coactivators/Ubiquitin Pathway Enzymes in Mammary Gland Tumorigenesis

Abstract

Steroid hormones, estrogen and progesterone, and their intracellular receptors play an important role in the development and progression of breast cancer. Coactivator proteins modulate the biological activity of these hormone receptors. We have cloned an E3 ubiquitin- protein ligase enzyme, E6-associated protein (E6-AP) as coactivators of steroid hormone receptors. The purpose of this research is to explore the possibility that the altered expression of E6-AP may contribute to the development of breast cancer. We have examined this possibility by studying the expression patterns of E6-AP and estrogen receptor-alpha (ERa) in various human breast cancer cell lines and breast tumor biopsy samples. Additionally, we have correlated the expression profile of E6-AP with that of ER in breast tumor biopsies. To date, we have examined 13 samples by immunhistochemistry, and 19 samples by Immunofluorescence. We found an inverse correlation between the expression of E6-AP and the expression of ER in these tumors. Furthermore, E6-AP is down regulated in invasive breast tumors compared with their adjacent normal tissues. These data suggest a possible role of E6-AP in mammary gland development and tumorigenesis. Presently, we are studying the expression profile of E6-AP and ER in different stage tumors. Our next goal of this project is to create novel in vitro models in stable cell lines, which will overexpress E6-AP.

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 2003
Accession Number
ADA417925

Entities

People

  • Xiuhua Gao
  • Zafar Nawaz

Organizations

  • Baylor College of Medicine

Tags

DTIC Thesaurus Topics

  • Androgen Receptors
  • Breast Cancer
  • Carrier Proteins
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Epithelial Cells
  • Glands
  • Hormones
  • Mammary Glands
  • Molecules
  • Neoplasms
  • Prostate Cancer
  • Proteins
  • Sex Glands
  • Tumor Cell Line

Fields of Study

  • Biology

Readers

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