CARD9 Promotes Sex-Biased Colon Tumors in the APCmin Mouse Model.
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.
Laboratory of Inflammation Biology, National Cancer Centre, Singapore, Singapore.
Vonny I
VI
Leo
Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre, Singapore, Singapore.
Sze Huey
SH
Tan
Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München, Münich, Germany.
Hanna
H
Bergmann
Department of Colorectal Surgery, Singapore General Hospital, Singapore, Singapore. Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore. Duke-NUS Graduate Medical School, National University of Singapore, Singapore, Singapore.
Peh Yean
PY
Cheah
Department of Colorectal Surgery, Singapore General Hospital, Singapore, Singapore.
Min Hoe
MH
Chew
Department of Pathology, Singapore General Hospital, Singapore, Singapore.
Kiat Hon
KH
Lim
Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München, Münich, Germany.
Jürgen
J
Ruland
Laboratory of Inflammation Biology, National Cancer Centre, Singapore, Singapore. patrick.reilly@nccs.com.sg.
Patrick T
PT
Reilly
D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D012727:Sex Characteristics
D016207:Cytokines