ER-α36 Interactions With Cytosolic Molecular Network in Acquired Tamoxifen Resistance

According to the World Health Organization (WHO) published data in 2015; breast cancer is the most prevalent and the second leading cause of cancer death among females. As approximately 70% of breast cancer tumor cells are estrogen receptor (ER) positive, primary therapeutic agents such as Anti-estrogens were produced mostly in a way to target this receptor. Anti-estrogen therapies mostly target Estrogen receptor and block its underlying signaling pathways. Nevertheless, resistance to these agents made the condition more complicated. Recently the role of one molecule in the resistance development has been studied in some cases: ER-α36 is a 36 kDa variant of estrogen receptor molecule which is mostly absent in normal breast cells. Its interactions with epidermal growth factor receptors and ER-α66 leads in over-activation and/or over-expression of estrogen-independent pathways and suppression of estrogen-dependent pathways; they all in turn, will maintain tumor cell's growth even in the presence of tamoxifen. In this mini-review, we mainly surveyed different pathways which ER-α36 could lead to tamoxifen resistance. We also briefly mentioned how ER-α36 could switch the growth cascades from estrogen dependent into independent and make this resistance network become even more complicated.