Morphologic transformation of human breast epithelial cells MCF-10A: dependence on an oxidative microenvironment and estrogen/epidermal growth factor receptors

Changes in levels of phenol red (PHR), hydrocortisone (HC), and epidermal growth factor (EGF) with or without estrogen treatment indicated that both oxidative stress- and estrogen receptor alpha (ERα)-mediated pathways contribute to cell transformation. Gene array and Western blotting analyses of cells maintained in our laboratory and of those from other sources documented detectable ERα and ERbeta (ERβ) in this ERα-negative cataloged cell line. Results also indicate the possibility of a direct association of EGF receptor (EGFR) and ERα in these cells as well as the formation and high induction of a novel ternary complex that includes ERβ (ERα/ERβ/EGFR) in cells grown under conditions facilitating transformation.Our studies resulted in the development of a growth protocol where the effects of chronic, physiologically relevant alterations in the microenvironment on cellular transformation were examined. From our results, we were able to propose a model of transformation within the MCF-10A cell line in which oxidative stress, ER and EGFR play essential roles. Overall, our work indicates that the immediate microenvironment of cells exerts powerful growth cues which ultimately determine their transformation potential.Breast cancer is one of the most common malignancies affecting women in Western countries [1]. Despite extensive research efforts worldwide at understanding and eradicating breast cancer, the cellular processes that lead to the onset of mammary carcinogenesis have yet to be definitively elucidated. Oxidative stress has come under increasing scrutiny in recent years as a causative factor in mammary carcinogenesis. Chronic infection and inflammation, which lead to reactive oxygen species (ROS) generation, are recognized risk factors for cancer development [2]. 17β-Estradiol (E2) [3-6] and epidermal growth factor (EGF) [7,8], two agents that can increase intracellular oxidative stress, are also strongly linked to the development of breast cancer. E2 binding to