RNA-seq of ER+ Breast Cancer xenografts under estrogen withdrawal

The goal of this study was to investigate transcriptional changes in clinically dormant, residual ER+ breast tumor cells that can survive extended periods of estrogen withdrawal (EW). To accomplish this, we grew either MCF-7 or HCC-1428 xenografts in ovariectomized, JNu mice with estrogen supplementation in the form of a subcutaneous 17-β-estradiol pellet. Once tumors reached appropriate volumes (400mm3), estradiol supplementation was removed, simulating anti-estrogen therapy via aromatase inhibition. Upon EW, xenografts regress rapidly to a non-palpable state within a period of 2-3 weeks. However, a proportion of cells survive this extended EW and do so in a clinically dormant state, which is stable for over 1 year. Thus, we harvested tumors after 0, 6, and 90 d of EW for RNA-seq analysis. To determine transcriptional changes associated with dormancy, we focused on genes deferentially expressed in clinically dormant tumor cells (90 d EW) compared to baseline (0 d EW ) that were unaffected by acute EW (6 d EW).