Cancers, Vol. 13, Pages 3612: Estrogen Receptor-Alpha and p53 Status as Regulators of AMPK and mTOR in Luminal Breast Cancer

Cancers, Vol. 13, Pages 3612: Estrogen Receptor-Alpha and p53 Status as Regulators of AMPK and mTOR in Luminal Breast Cancer Cancers doi: 10.3390/cancers13143612 Authors: Nishant Gandhi Chetan C. Oturkar Gokul M. Das Luminal breast cancer (LBC) driven by dysregulated estrogen receptor-alpha (ERα) signaling accounts for 70% of the breast cancer cases diagnosed. Although endocrine therapy (ET) is effective against LBC, about one-third of these patients fail to respond to therapy owing to acquired or inherent resistance mechanisms. Aberrant signaling via ERα, oncogenes, growth factor receptors, and mutations in tumor suppressors such as p53 impinge on downstream regulators such as AMPK and mTOR. While both AMPK and mTOR have been reported to play important roles in determining sensitivity of LBC to ET, how the ERα-p53 crosstalk impinges on regulation of AMPK and mTOR, thereby influencing therapeutic efficacy remains unknown. Here, we have addressed this important issue using isogenic breast cancer cell lines, siRNA-mediated RNA knockdown, and different modes of drug treatments. Interaction of p53 with ERα and AMPK was determined by in situ proximity ligation assay (PLA), and endogenous gene transcripts were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Further, the effect of concurrent and sequential administration of Fulvestrant–Everolimus combination on colony formation was determined. The studies showed that in cells expressing wild...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research