1329 GENOME-WIDE EFFECTS OF PROSTATE CANCER ON DENDRITIC CELLS IN THE MURINE MODEL

Autor:	Georgi Guruli, Blake W. Moore, Ekaterine Goliadze, P. Joseph Yannie, MaryEllen T. Dolat, Jeffrey Wolters, Alberic Rogman
Rok vydání:	2013
Předmět:	Programmed cell death business.industry Urology medicine.disease Proinflammatory cytokine Prostate cancer Real-time polymerase chain reaction medicine.anatomical_structure Downregulation and upregulation Apoptosis Prostate Cancer research Medicine business Endothelin receptor
Zdroj:	Journal of Urology. 189
ISSN:	1527-3792 0022-5347
Popis:	INTRODUCTION AND OBJECTIVES: The apoptotic and suppressive effects of prostate cancer on immune-competent cells are well known. The aim of this study was to evaluate the genome-wide effects of prostate cancer on dendritic cells (DC), the most effective antigenpresenting cells, in a murine prostate cancer model. METHODS: Dendritic cells were compared to DC incubated with RM-1 murine prostate cancer cells. Affymetrix Mouse 430 v2 Array was used for analysis containing 45000 probes. Quantitative polymerase chain reaction (qPCR) was performed to validate changes in the endothelin axis. RNAs from murine prostate cancer and normal murine prostate were also compared. RESULTS: There was a significant increase in the expression of cell death inducing genes in DC incubated with prostate cancer cells, including multiple caspases. There was also a down regulation of proinflammatory genes including a number of interleukins and interferons. A change in the expression of endothelin receptors was seen as well. Considering the role of the endothelin axis in DC functioning, we used qPCR to further evaluate the condition of the endothelin axis in DC under prostate cancer influence. There was a significant decrease in the expression of ET-1 (4.50 1.33 fold) and ETA receptor (2.67 0.13), which are involved in DC survival and pro-inflammatory function. There was also an increase in the expression of ETB receptor (3.42 0.14) involved in DC apoptosis. Genome-wide comparison of RNAs derived from murine prostate cancer and murine prostate further demonstrated decreased expression of apoptotic genes by prostate cancer cells. CONCLUSIONS: Prostate cancer induces a wide variety of changes in DC including decreased expression of genes responsible for pro-inflammatory function and survival. Alterations of the endothelin axis may be one reason why tumor escapes immune monitoring.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::e7eedce58334ef8714caf8ceeeee2268 https://doi.org/10.1016/j.juro.2013.02.2683 Zobrazit plný text záznamu