Growth-Promoting and Angiogenic Functions of Adenosine in Breast Cancer
Annual rept. 1 Aug 2001-31 Jul 2002
NORTH CAROLINA UNIV AT CHAPEL HILL
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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.
- Anatomy and Physiology
- Medicine and Medical Research