Correlation Between the Composition of Various Estrogen Receptors and Ligand Binding
Annual rept. 25 Sep 2001-24 Sep 2002
HOWARD UNIV WASHINGTON DC
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Clinical data show that about 50 of the ER-positive patients respond to tamoxifen, the most widely used anti- estrogen. The factors that correlate with resistanceresponse to tamoxifen, or any other anti-estrogens, are largely not understood, but are likely to depend on the relative amounts of all ER forms present in the tumor tissue. Therefore, lack of knowledge of the correlation between the relative amounts of various ER isoforms with response is an important problem, because, without it, identification of patients who are most likely to respond to a particular anti-estrogen therapy is not possible. In the current study, we are testing the hypothesis that total ER isoform composition correlates with both ligand estrogen or tamoxifen and DNA binding properties using different cancer cell lines. Our results indicate that the three cell lines analyzed so far are distinct in their ER isoform composition. Although MCF-7 and T47D show similar binding to estrogen, they-have distinct tamoxifen binding. ZR-75 cells have relatively high levels of ER alpha exon deletion variants and show lower binding to estrogen and relatively even less binding to tamoxifen. The DNA binding properties of the three cells lines are similar.
- Anatomy and Physiology
- Medicine and Medical Research