Abstract C023: Aryl hydrocarbon receptor and leptin promote prostate cancer progression and may be associated with chemoresistance

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 AhR protein is overexpressed and constitutively active in castration-resistant PCa cells. AhR signaling is promoted by high fat diet-induced obesity, when circulating leptin levels are also high. Physiologically relevant leptin concentration is proportional to BMI and is secreted by adipose cells to inhibit hunger under normal circumstances. Our preliminary results suggest that both AhR and leptin independently desensitize PCa cells to clinically-relevant chemotherapeutics however, the underlying mechanisms must be elucidated and may require sustained AhR signaling. We also 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). 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 exacerbated in the presence of both leptin and AhR. Further understanding of the potential interactions between diet-induced obesity and chemoresistance can promote improved treatments for patients. Citation Format: Kofi K. Khamit-Kush, Joann B. Powell, Jeffrey A. Handy, Nathan J. Bowen, Valerie Odero-Marah, Daqing Wu. Aryl hydrocarbon receptor and leptin promote prostate cancer progression and may be associated with chemoresistance [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C023.