The file is restricted for YU community access only.
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.