Understanding Endocrine Resistance in Breast Cancer

Abstract

Approximately two-thirds of breast cancers are dependent on estrogen, underscoring the importance of estrogen for disease progression. Breast cancer progression is also regulated by the mTORC1 signaling pathway. This work sets out to establish whether positive cross-talk between the mTORC1 and Estrogen Receptor (ER)α pathways is the basis of the growth advantage of ERα-positive breast cancer cells, and is the driving mechanism for ligand-independent ERα activation and endocrine therapy escape. Studies of TOS motif comparison, Immunoprecipitation assays, and Immunoflorecense were considered. The results of the TOS motif comparison found the five amino acid sequence that ERα has to be a comparable TOS motif of other proteins regulated by mTOR and extend across evolutionarily closely related species. When testing whether interaction between ERα and Raptor exists, the complex includes mTOR. Accordingly, we established a direct link between the mTORC1 and ERα signaling pathways. Through our experiments, it is established that connections between the mTORC1 and ERα pathways contribute to cross-talk in control of endocrine therapy sensitivity and emergence of resistance. Hopefully, with this advanced understanding and continued investigation, we will be able to develop specific targeted therapy to prevent endocrine therapy escape.