CARD9 Promotes Sex-Biased Colon Tumors in the APCmin Mouse Model

Abstract

Caspase recuitment domain-containing protein 9 (CARD9) functions in different inflammation pathways to elicit responses to microbial signals and is known to affect intestinal inflammation. Examining the APC min mouse model of intestinal tumorigenesis and using stringently controlled, sex-and age-matched pairs of CARD9-competent and CARD9-deficient mice, we have found that CARD9 has a restricted but strong effect on tumorigenesis in the large intestine. We have found that CARD9 reduces viability specifically in males and promotes tumorigenesis specifically in the large intestines of these male mice. To our knowledge, this is the first gene ablation in APC min mice that solely affects colon tumors in male subjects and, as such, may have significant clinical implications. Additional data suggest correlative disruption of plasma cytokine expression and immune infiltration of the tumors. We speculate that known sex-specific differences in human colorectal cancer may involve inflammation, particularly CARD9-dependent inflammation. Cancer Immunol Res; 3(7); 721-6. Ó2015 AACR.

CARD9 prevents lung cancer development by suppressing the expansion of myeloid‐derived suppressor cells and IDO production

“…find an ectopic overexpression of CARD9 in gastric B‐cell lymphoma. Leo et al . demonstrate that CARD9 promotes sex‐biased colon tumors in the adenomatous polyposis coli multiple intestinal neoplasia (APC min ) mouse model.…”

“…Nakamura et al 4 find an ectopic overexpression of CARD9 in gastric B-cell lymphoma. Leo et al 30 demonstrate that CARD9 promotes sex-biased colon tumors in the adenomatous polyposis coli multiple intestinal neoplasia (APC min ) mouse model. Our recently study on colitis-associated colon cancer confirms a critical role of CARD9 in colon cancer.…”

Effects of a Grapevine Shoot Extract Containing Resveratrol and Resveratrol Oligomers on Intestinal Adenoma Development in Mice: In Vitro and In Vivo Studies

“…That being said, a diminished hematocrit and an increased spleen as well as liver weight are expected outcomes in Apc Min mice fed a high‐fat diet . There are a few studies describing gender‐dependent effects on adenoma development in mice carrying a mutation in the APC gene, which are, for example, related to factors such as physical exercise or genotype . Nevertheless, the specific reason for the observation that Vineatrol®30 is more effective in male animals remains elusive.…”

Caspase Recruitment Domain Containing Protein 9 Suppresses Non-Small Cell Lung Cancer Proliferation and Invasion via Inhibiting MAPK/p38 Pathway

“…The elevation of CARD9 mRNA in gastric B-cell lymphoma [6] indicated that CARD9 was related with tumorigenesis and development. CARD9 can promote tumorigenesis of large intestines in the male APC min mice, which mimics the genetic lesions associated with human familial adenomatous polyposis [7]. In addition, upregulation of CARD9 was also found in renal cell carcinoma and was significantly associated with poor prognosis [8].…”