Abstract 394: Elevated aryl hydrocarbon receptor and leptin receptor expression correlates with prostate cancer progression and may be associated with obesity-associated leptin-mediated chemoresistance

Abstract

Abstract The aryl hydrocarbon receptor (AhR) is a nuclear transcription factor and xenobiotic sensor reported to mediate diet-induced obesity and is upregulated in high-grade prostate cancer (PCa). Previously published data from our lab shows that AhR protein is overexpressed and constitutively active in castration-resistant prostate cancer cells. Physiologically relevant leptin concentration is proportional to BMI and it is secreted by adipose cells to inhibit hunger under normal circumstances. Our preliminary results suggest that obesity-associated leptin concentrations desensitize PCa cells to cancer drugs however, the underlying mechanisms must be elucidated and may require sustained AhR signaling. In this study, we conducted an integrative bioinformatics analysis to explore the role of AHR and LEPR in PCa, which revealed AHR and LEPR mRNA expression positively correlates in prostate cancer (P<0.05, Pearson: 0.68, R^2=0.46). The mRNA expression levels of AHR and LEPR in PCa tissue samples (i.e. solid tissue normal samples from individuals with cancer in TCGA, N=498) were analyzed using the cBioPortal and Xena online tools. We will further investigate if the decrease in drug response is seen in the presence of obesity-associated leptin concentrations. Further understanding of the potential interaction(s) between adipokines, AhR, and chemoresistance can promote improved treatments for patients with prostate cancer. Citation Format: Kofi Kyenku Khamit-Kush, Joann B. Powell, Jeffrey A. Handy, Nathan Bowen, Daqing Wu, Valerie Odero-Marah. Elevated aryl hydrocarbon receptor and leptin receptor expression correlates with prostate cancer progression and may be associated with obesity-associated leptin-mediated chemoresistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 394.