Abstract A12: Expression of GPR41, GPR43, and GPR109A in breast tissue in relation to breast cancer development

Abstract

Abstract Introduction: There is evidence to suggest that the human microbiome may play a key role in the development of breast cancer. There is a unique microbial signature in mammary tissue that is associated with breast cancer. Further, there is mounting evidence to support the role of the gut microbiome in promoting or preventing breast cancer. Consequently, specific compositional and/or functional shifts in either of these microbiomes may promote the growth of breast tumors. Short chain fatty acids (SCFAs) are microbial metabolites produced in the large intestine by bacterial fermentation of complex carbohydrates. These metabolites exit the gut and interact with many different cell types throughout the human body, including those in the breast, via g-protein coupled receptors; GPR41, GPR43, and GPR109A. These metabolites have been identified as a potential functional connection between the gut microbiome and breast cancer but have not been studied in breast tissue in the context of breast cancer. To assess the interaction between the microbiome and breast tumor development, we analyzed the expression of these receptors in tissue collected from women who donated healthy, prediagnostic, or cancerous tissue to the Susan G. Komen and Indiana University Simon Cancer Center Tissue Banks. Methods: DNA and RNA (n=60, n = 15 for each tissue subset: healthy, prediagnostic, adjacent normal, and tumor tissue) was copurified from these tissues using the Qiagen AllPrep® PowerFecal® DNA/RNA Kit. The RNA was then reverse transcribed into complementary DNA. Quantitative PCR was performed on the cDNA using four validated primer sets: GPR41, GPR43, GPR109A, and ribosomal 18S (housekeeping gene). Results/Cconclusions: We did not identify any significant differences in expression levels of these receptors between the participant groups, suggesting that cancer status is not associated with increased metabolic activity of the microbiome. We are currently conducting sensitivity analyses to determine the role of clinical factors such as age, menopausal status, BMI, etc., on the expression of these receptors in breast tissue. We are also investigating the expression of enzymes and transporters in breast tissue related to host cell metabolism of the most bioactive SCFAs (acetate, propionate, and butyrate). This work will yield valuable information regarding the interaction between the human microbiome and breast tumor development. Ultimately, it may be possible to target SCFA-producing bacteria or SCFA catabolic pathways in breast tissue to prevent or treat breast cancer. Citation Format: Annie Kump, Daniel Herrera, Leah T. Stiemsma. Expression of GPR41, GPR43, and GPR109A in breast tissue in relation to breast cancer development [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A12.