Aberrant Homeobox Gene Expression in Mammary Tumorigenesis

Abstract

We hypothesized that aberrant expression of Hox genes in mammary epithelial cells results in the inappropriate regulation of a wide variety of Hox target genes; this could lead to a change from a normal to a preneoplastic, or from a preneoplastic to a neoplastic phenotype. The purpose is to test this hypothesis by manipulating the expression of Hox genes such as Hoxa1, Hoxa3, or Hoxa11 in cells from hyperplastic (preneoplastic) lesions of the breast by employing a tetracycline regulated vector system. The cells will be assayed for growth, response to retinoic acid (RA), and their expression of markers of the neoplastically transformed state. The goals' of this research are: (1) to understand the functions of homeobox genes in normal and neoplastically transformed mammary epithelial cells; (2) to ascertain whether or not the overexpression of homeobox genes results in a neoplastic phenotype; and (3) to assess whether these Hox gene overexpressing cells respond to exogenous RA. In the past year we, have analyzed both p53 +/+ and p53 -/- breast tumors for Hox gene expression. In addition, we have examined mouse mammary glands (normal and preneoplastic) for Hox gene expression. The significance is that this new information may be employed to develop novel methods for regulating homeobox gene expression as a therapy for human breast cancer.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2001
Accession Number
ADA403389

Entities

People

  • Lorraine J. Gudas

Organizations

  • Weill Cornell Medicine

Tags

DTIC Thesaurus Topics

  • Acids
  • Anti-Bacterial Agents
  • Breast Cancer
  • Cancer
  • Cell Line
  • Cells
  • Culture Techniques
  • Cultured Cells
  • Epithelial Cells
  • Gene Expression
  • Gene Therapy
  • Genetics
  • Neoplasms
  • New York
  • Retinoic Acids
  • Stem Cells

Fields of Study

  • Biology
  • Medicine

Readers

  • Molecular Biology and Genetics