NF-κB signaling promotes castration-resistant prostate cancer initiation and progression.

Prostate Cancer (PCa) is the second leading cause of cancer-related death in men. Adenocarcinoma of the prostate is primarily composed of Androgen Receptor-positive (AR) luminal cells that require AR transcriptional activity for survival and proliferation. As a consequence, androgen deprivation and anti-androgens are used to treat PCa patients whose disease progresses following attempted surgical or radiation interventions.

IL-1-conferred gene expression pattern in ERα BCa and AR PCa cells is intrinsic to ERα BCa and AR PCa cells and promotes cell survival.

Background: Breast (BCa) and prostate (PCa) cancers are hormone receptor (HR)-driven cancers. Thus, BCa and PCa patients are given therapies that reduce hormone levels or directly block HR activity; but most patients eventually develop treatment resistance. We have previously reported that interleukin-1 (IL-1) inflammatory cytokine downregulates ERα and AR mRNA in HR-positive (HR) BCa and PCa cell lines, yet the cells can remain viable.

RELA is sufficient to mediate interleukin-1 repression of androgen receptor expression and activity in an LNCaP disease progression model.

Background: The androgen receptor (AR) nuclear transcription factor is a therapeutic target for prostate cancer (PCa). Unfortunately, patients can develop resistance to AR-targeted therapies and progress to lethal disease, underscoring the importance of understanding the molecular mechanisms that underlie treatment resistance. Inflammation is implicated in PCa initiation and progression and we have previously reported that the inflammatory cytokine, interleukin-1 (IL-1), represses AR messenger RNA (mRNA) levels and activity in AR-positive (AR ) PCa cell lines concomitant with the upregulation of prosurvival biomolecules.