Determining the role played by Aryl Hydrocarbon Receptor (AHR) in the colon carcinoma tumor model

Author

Poonam Yakkundi, University of the PacificFollow

Date of Award

2018

Document Type

Dissertation

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Pharmaceutical and Chemical Sciences

First Advisor

William K. Chan

First Committee Member

Mark J. Selby

Second Committee Member

Maria Galou-Lameyer

Third Committee Member

John C. Livesey

Fourth Committee Member

Miki S. Park

Abstract

Aryl hydrocarbon receptor (AHR), commonly known as an environmental sensor involved in the metabolism and elimination of xenobiotic substances, is also an important modulator in the development and functioning of the immune system. AHR expression is varied in the T cell subsets with the highest expression in T-helper 17 and T regulatory cells. Work from many researchers has suggested that AHR can act as a tumor promoter or a tumor suppressor depending on the tumor type. Our goal is to understand the role played by AHR in MC38 syngeneic colon carcinoma tumor model. In the absence of AHR, MC38 tumor progresses by an increase in tumor associated macrophages (TAMs), M2 macrophages and a decrease in CD8a positive cytotoxic lymphocytes. Analysis of the intratumoral cytokines reveals a pro-inflammatory phenotype. This has been assessed by pharmacologic blocking of the receptor using CH223191 and in AHR deficient (AHR-/-) mice. Therefore AHR acts as a tumor suppressor gene in colon carcinoma tumor model and silencing it may lead to colon cancer progression.

Pages

141

Recommended Citation

Yakkundi, Poonam. (2018). Determining the role played by Aryl Hydrocarbon Receptor (AHR) in the colon carcinoma tumor model. University of the Pacific, Dissertation. https://scholarlycommons.pacific.edu/uop_etds/3571