The effect of IKKβ on estrogen receptor positive breast cancer phenotypes

Estrogen receptor α (ER) is a good prognostic marker expressed in ~75% of breast tumors. Women with ER+ tumors will receive endocrine therapy, yet ~50% will experience relapse and late recurrence ~5-20 years after primary diagnosis. The recurrent tumors are often aggressive, resistant, and metastatic. A growing body of evidence suggests that an inflammatory microenvironment and the activation of the NF-ĸB pathway are highly associated with the progression of ER+ tumors to more aggressive stages. However, it is unknown whether NF-ĸB is a driver or a consequence of aggressive ER+ disease. In order to study this, we developed multiple ER+ breast cancer cell lines expressing a Doxycycline-inducible, constitutively active form of IĸB kinase β (CA-IKKβ), a key kinase in the canonical NF-ĸB pathway. This allowed us to specifically activate the canonical arm of the NF-ĸB pathway in a controlled fashion. Constitutively active IKK β-MCF-7 cells are treated with Estrogen (E2), Doxycycline (Dox) or E2+Dox for 72 hrs.The study includes four groups: Vehicle, E2, Dox and E2+Dox with three replicates per group.