Growth-Promoting and Angiogenic Functions of Adenosine in Breast Cancer

Abstract

Adenosine is a potential novel factor in breast cancer progression and this project has been designed to evaluate adenosine tumor-promoting activity experimentally. The initial period (12 months, Aug 1, 2001 to Jul 31, 2002) has been used to generate and characterize breast cancer cell lines that differ in adenosine removing and generating potency. We have accomplished these goals successfully and altered invasive and metastatic MDA-MD-231 cells that have a high rate of endogenous adenosine generation. Using retroviral gene transfer system we generated variants that: a) overexpress adenosine deaminase (ADA), an enzyme that removes endogenous adenosine, b) exhibit decreased expression of ecto-5'-nucleotidase (eN) with anti-sense cDNA, and c) overexpress EGFP, a control protein. All these cells have been cloned by limited dilution and their altered adenosine metabolism has been analyzed, and confirmed, in vitro. Furthermore, we used MCF-7 cells that are non-tumorigenic and do not express endogenous eN, to develop eN-expressing and EGFP-expressing variants. We have obtained control EGFP cells and are currently selecting for the eN-expressing clones. Thus, we are in position to initiate the second phase of the project and test selected cells for their angiogenic and tumorigenic potential in nude mice.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2002
Accession Number
ADA411431

Entities

People

  • Jozef Spychala

Organizations

  • University of North Carolina at Chapel Hill

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Adenosine
  • Antigens
  • Biomedical Research
  • Breast Cancer
  • Cell Line
  • Cells
  • Culture Techniques
  • Diseases And Disorders
  • Enzymes
  • Lymphocytes
  • Medical Personnel
  • Neoplasms
  • North Carolina
  • Proteins
  • Tissue Extracts
  • Tumor Cell Line

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics
  • Parasitology and Pharmacology of Malaria.