Deregulation of E‐Cadherin and MTA2 in Tamoxifen Resistant Breast Cancer Cells

Abstract

Tamoxifen is an antiestrogen often used to treat hormone responsive breast cancer. It is a selective estrogen receptor modulator that inhibits breast cancer cell growth by competing with estrogen for receptor binding. Although tamoxifen has been successful in the treatment of breast cancer, prolonged usage of the drug often leads to the development of acquired resistance in which tumors become non‐responsive. Previously, our lab demonstrated that tamoxifen resistant breast cancer cells exhibit an increased ability to proliferate even in the presence of the antagonist. In addition to changes in growth characteristics, recent analysis suggest that tamoxifen resistant cells also develop more aggressive phenotypes, including the ability to migrate and invade through the extracellular matrix. Our data also suggest that these resistant cells express lower levels of E‐cadherin and higher levels of metastasis associated protein 2 (MTA2). Furthermore, our preliminary results indicate that DNA methylation may be responsible for the down regulation of E‐cadherin, however its role in MTA2 expression requires further investigation. The development of acquired resistance to tamoxifen and other anti‐estrogens has been a major obstacle in breast cancer therapy, and understanding how the deregulation of E‐cadherin and MTA2 contribute to the development of resistance will offer some insights to this problem.