Up-regulation of cyclin E in breast cancer via estrogen receptor pathway.

It is well known that cell cycle dysregulation plays an important role in breast cancer. The mechanism, however, is not fully understood. In this study, we aimed to explore whether estrogen and estrogen receptor pathway play a role in the regulation of cell cycle protein cyclin E expression, and whether the expression of cyclin E is associated with breast cancer prognosis. We first examined the level of cyclin E expression in breast cancer by immunohistochemistry. Benign fibroadenoma was used as controls. Next we cultured MCF-7 cells with different concentration of 17β-estradiol or tamoxifen for 48 hours. Then we employ qRT-PCR to determine changes of cyclin E in MCF-7 cells. Cyclin E is overexpressed in breast cancer and its expression is associated with the status of estrogen receptor and lymph node metastasis. After treatment with 17β-estradiol, the gene expression of cyclin E was enhanced, and as the concentration increased, the enhancement increased. After treatment with tamoxifen, the gene expression of cyclin E was inhibited, and as the concentration decreased, the inhibition increased. We demonstrated that estrogen induces, while tamoxifen inhibits cyclin E expression. This indicate that estrogen receptor pathway play a critical role in cell cycle dysregulation in breast cancer.