Tamoxifen pathway and possible mechanisms of endocrine resistance in breast cancer cells

The tamoxifen pathway and possible mechanisms of endocrine resistance in breast cancer cells. Prior to entering the breast cancer cell, tamoxifen (T) is metabolized in the liver into the two active metabolites, endoxifen and 4-hydroxytamoxifen (4-OHT). When these metabolites enter the cell (blue background) they can bind to estrogen receptors (ERs), thereby blocking the binding of estrogen. ERs bound to tamoxifen then dimerize, enter the nucleus and bind to estrogen response element (ERE). However, the necessary coactivators will not be recruited by the ER–tamoxifen complex. Only corepressors are recruited, therefore gene transcription is not activated. In tamoxifen resistance, this blocking is compromised due to several possible mechanisms: e.g., changes in activity of the metabolizing enzymes of tamoxifen, loss or modification of ER expression, alternative signaling pathways for proliferation and growth, and alterations in the balance of co-regulatory proteins and altered expression of microRNAs [,]. Black arrow: normal estrogen pathway. Blue arrow: tamoxifen pathway. Crossed arrow: disrupted pathway.

Publication

The Role of MicroRNAs as Predictors of Response to Tamoxifen Treatment in Breast Cancer Patients. (2015) Nina G. Egeland, et al. Int J Mol Sci. 2015 Oct;16(10):24243-24275. Figure: F3. All organisms Mus musculus Homo sapiens Drosophila melanogaster

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