Long-term exposure of 4-hydroxyestradiol induces the cancer cell characteristics upregulating CYP1B1 in MCF-10A cells.

Life-long estrogen exposure is one of the major risk factors in the development and progression of breast cancer. However, little is known about the molecular mechanisms, by which chronic exposure to estrogen contributes to breast carcinogenesis. The aim of the present study was to investigate the effects of long-term exposure with 4-hydroxyestradiol (4-OHE) on acquired cancer characteristics of human mammary epithelial MCF-10A cells. The possible regulators were further studied in chronic 4-OHE-treated MCF-10A cells. We observed that MCF-10A cells long-term exposed to 4-OHE acquire the characteristics of cancer cells, such as enhanced cell growth, EMT properties, and increased migration and invasiveness. Moreover, the expression of CYP1B1 was significantly elevated in long-term 4-OHE-treated MCF-10A cells. Block of CYP1B1 significantly reduced the cancer cell characteristics in long-term 4-OHE-treated MCF-10A cells. Our results indicated that 4-OHE mediated enhanced cancer cell characteristics in mammary epithelial cells are an important key event for breast carcinogenesis process. CYP1B1 partially contributes to the 4-OHE induced cancer cell characteristics in MCF-10A cells. Targeting CYP1B1 might offer a new strategy for the treatment of estrogen-induced breast cancer.