Estrogen receptor DNA binding is not required for estrogen-induced breast cell growth

In this study, we determined whether ER DNA binding is necessary for estrogen to stimulate the growth of breast cancer cells. To investigate the requirement of ER DNA binding we expressed either wild-type or a DNA-binding mutant ER alpha in a clone of the MCF-7 breast cancer cell line that no longer expressed endogenous ER alpha. Estrogen did not activate non-genomic kinase cascades in the parental MCF-7 cells or in cells expressing ER alpha mutant. In cells expressing the ER alpha mutant, estrogen did not induce ERE dependent gene expression but did induce AP-1- and Sp 1-dependent gene expression and the cell cycle regulatory genes cyclin D1 and c-myc. However, we demonstrated that estrogen still induced cell proliferation in MCF-7 cells expressing the ERa mutant. These results demonstrate that ER DNA binding is not absolutely required for estrogen to induce breast cancer cell growth. (c) 2007 Elsevier Ireland Ltd. All rights reserved.