Session: S74-Bench to Bedside: Cellular Signaling and Regulation of Steroid Receptor Function
Room 303 (Moscone Center)
Elevated phosphorylation of estrogen receptor alpha (ERá) is associated with favorable outcome for endocrine adjuvant therapy. It is possible that reduced phosphorylation could disrupt ERá signaling and impact tumor growth. ERá+ MCF-7 breast cancer cells engineered to stably express reduced phosphorylation at sites S118 or S167 exhibited increased growth/migration/invasion and altered estradiol-regulated gene expression in vitro. However, cells retained sensitivity to growth inhibition by tamoxifen and ICI 182,780. Artificial light at night is classified as a "probable human carcinogen". Extending this concept to endocrine therapy resistance in breast cancer, rats implanted with “tissue-isolated” MCF-7 xenografts were housed in light boxes at 12L:12 dark or exposed to dim light (0.2 lux) during the dark phase. Dim light exposure resulted in increased tumor growth and tamoxifen resistance. ERá phosphorylation and tumor proliferative/survival pathways were elevated. Collective results on ERá phosphorylation and circadian disruption will be discussed with regard to endocrine therapy resistance.
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