The Role of the JNK/Jun Signaling Node in ERα+ Breast Cancer Cell Survival and Autophagy

Abstract

A common treatment for estrogen receptor positive breast cancers is the use of selective estrogen receptor modulators such as Tamoxifen [1]. Unfortunately, 30-40% of patients experience relapse due to the development of antiestrogen resistance [2]. Autophagy, a process that is typically seen in cells that are exposed to a variety of stresses, is critical to the development of antiestrogen resistance and may play a key role in metastatic progression [3, 4]. To further combat antiestrogen resistance, a potential target for breast cancers is JNK (c-Jun N-terminal kinase), a member of the mitogen-activated protein kinase (MAPK) family. Our hypothesis is that JNK is a key regulator of autophagy and the emergence of autophagy-dependent antiestrogen resistant breast cancer. JNK-IN-8 was used for all experiments in this thesis proposal which tests the hypothesis that JNK1/2 is a key regulator of autophagy and the emergence of autophagy-dependent antiestrogen resistant breast cancer. The aims are to utilize ER+ breast cancer cells and determine (1) the effect of JNK1/2 inhibition on cell death under conditions of estrogen (E2) supplementation and antiestrogen treatment (+/- 4-OHT) and (2) the effect of JNK1/2 inhibition on autophagy. These studies have the potential to identify the JNK1/2/Jun signaling node as a molecular target for the improved treatment of breast cancer.