Promoter and Cofactor Requirements for SERM-ER Activity

Abstract

The mechanisms of estrogen-mediated transcription are not completely understood and as such, the roles of Selective Estrogen Receptor Modulators (SERMs), such as tamoxifen are also poorly understood. Our current work is focused on assessing the relative contributions of the specific promoter sequences within estrogen target genes and how they influence the transcriptional activity by different ligands. Specifically, we have generated breast (MCF-7) and endometrial (ECC1) cancer cell lines with a Lox-Luciferase cassette integrated within the chromatin. These clonal cell lines have been screened by Southern blot and FISH to confirm the presence of a single integration site. Different promoter sequences from estrogen regulated genes have been introduced into these donor cell lines via Cre-mediated recombination. To insert these specific promoter sequences into the same site within the chromatin, we generated an insertion vector containing a multiple cloning sites flanked by Lox sites. After integration of the various promoter sequences we used negative selection to generate cell lines that contained the different promoter sequences within the same chromatin setting. These cell lines are currently being assessed for luciferase activity in the presence of different ligands.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2005
Accession Number
ADA435797

Entities

People

  • Jason S. Carroll

Organizations

  • Dana–Farber Cancer Institute

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Alkenes
  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Cassettes
  • Cell Line
  • Cells
  • Chromosome Structures
  • Estrogens
  • Growth Factors
  • Hormone Antagonists
  • Hormones
  • Modulators
  • Neoplasms
  • Proteins
  • Uterine Cancers

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular Genetics