Activation of NFkB is a novel mechanism of pro-survival activity of glucocorticoids in breast cancer cells

• GC/GR trans-activates NFkB in luminal subtype breast cancer cell MCF7.
• GC treatment increases the nuclear localization of p65/RelA.
• The interaction between p65/RelA and GR is decreased in response to GC/GR signaling.
• c-Myc as one of NFkB target genes is enhanced by GC/GR.
• GC/GR promotes MCF7 cell proliferation, different from the pro-apoptotic effect in hematopoietic cancers.

Glucocorticoids (GCs) are pro-apoptotic as a co-medication to treat leukemia and lymphoma. However, the effects in breast cancer (BC) are diverse with mechanisms less understood. In this study using BC model cell MCF7, we found that dexamethasone (Dex) promotes cell proliferation. Gene expression analysis identified that c-Myc was enhanced by Dex, providing an important link to the pro-survival effect of GCs in BC. Dex treatment promoted NFkB transcriptional activity leading to the up-regulation of c-Myc. RelA was activated by Dex but with decreased interaction with GR, thus identifying a new pattern of regulation of NFkB by GC/GR in BC cells.