Publications by authors named "Kimberly Buys"

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Determination of the Potential Tumor-Suppressive Effects of in a Chemically Induced and in a Genetically Modified Intestinal Cancer Mouse Model.

Cancers (Basel) 2019 Aug 20;11(8). Epub 2019 Aug 20.

Center of Medical Genetics, University of Antwerp, Prins Boudewijnlaan 43/6, Edegem, BE-2650 Antwerp, Belgium.

(), also known as () and previously identified to be an inducer of regulated cell death, is frequently epigenetically inactivated in different cancer types, suggesting that is a tumor suppressor gene. In this study, we aimed to evaluate the tumor-suppressive effects of GSDME in two intestinal cancer mouse models. To mimic the silencing of by methylation as observed in human cancers, a knockout (KO) mouse was developed. The effect of GSDME on tumorigenesis was studied both in a chemically induced and in a genetic intestinal cancer mouse model, as strong evidence shows that GSDME plays a role in human colorectal cancer and representative mouse models for intestinal cancer are available. Azoxymethane (AOM) was used to induce colorectal tumors in the chemically induced intestinal cancer model ( = 100). For the genetic intestinal cancer model, mice were used ( = 37). In both experiments, the number of mice bearing microscopic proliferative lesions, the number and type of lesions per mouse and the histopathological features of the adenocarcinomas were compared between KO and wild type (WT) mice. Unfortunately, we found no major differences between KO and WT mice, neither for the number of affected mice nor for the multiplicity of proliferative lesions in the mice. However, recent breakthroughs on gasdermin function indicate that GSDME is an executioner of necrotic cell death. Therefore, it is possible that GSDME may be important for creating an inflammatory microenvironment around the tumor. This is in line with the trend towards more severe inflammation in WT compared to KO mice, that we observed in our study. We conclude that the effect of GSDME in tumor biology is probably more subtle than previously thought.
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August 2019