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 ERα in a clone of the MCF-7 breast cancer cell line that no longer expressed endogenous ERα. Estrogen did not activate non-genomic kinase cascades in the parental MCF-7 cells or in cells expressing ERα mutant. In cells expressing the ERα mutant, estrogen did not induce ERE-dependent gene expression but did induce AP-1- and Sp1-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 ERα mutant. These results demonstrate that ER DNA binding is not absolutely required for estrogen to induce breast cancer cell growth.
- Breast cancer
- Cell growth
- Transcription factor crosstalk