Document Type

Conference Proceeding

Publication Date


Publication Title

J Invest Dermatol


The aryl hydrocarbon receptor(AhR) is a ligand-activated transcription factor that responds to chemical carcinogens. An endogenous AhR agonist, 6-Formylindolo[3,2-b]carbazole, is produced following ultraviolet light(UV) absorption by tryptophan. Epidemiological studies show a correlation between exposure to AhR agonists and non melanoma skin cancer(NMSC). As an example, AhR activation promotes metabolism of pro-carcinogens to carcinogens such as the metabolism of benzo(a)pyrene to benzo[a]pyrene diol epoxide(BPDE). There are differing epidemiological studies which explain the relationship between obesity and NMSC—some demonstrate a positive association while others demonstrate a negative association. However, evidence supporting an inverse correlation is relatively weak and heavily confounded by UV exposure among body mass index groups. Our objective was to determine the role of AhR in adipose tissue-stimulated malignant transformation. RNA-seq analysis demonstrated that secretions from adipocytes induced AhR-regulated phase I metabolizing enzymes in a non-tumorigenic, mouse epidermal cell line, JB6 P+, including CYP1A1 which metabolizes B[a]P to BPDE. Phase II detoxifying enzymes remained unchanged or reduced suggesting xenobiotic metabolism by adipocyte secretions. Together, B[a]P and adipocyte secretions induce malignant transformation, assessed by the JB6 P+ soft agar clonogenic assay. Primary human keratinocytes, cultured with adipocyte-conditioned medium for 24 hours, demonstrated elevated AhR protein levels and induction in CYP1A1 and CYP1B1 mRNA(3.6 and 10.2-fold)compared to the media control cells. Understanding how adipocytes modulate AhR activity in skin with or without environmental AhR ligands will lead to new therapeutic strategies to prevent epidermal cell transformation.





First Page




To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.