title: Carcinogen-induced skin tumor development requires leukocytic expression of the transcription factor Runx3.
abstract: Carcinogen-induced skin tumorigenesis depends heavily on proinflammatory tumor-promoting processes. Here, we show that leukocytic Runx3 expression is central to the two-stage DMBA/TPA-induced skin tumorigenesis. Runx3-null mice were highly resistant to this process and concomitant ablation of Runx3 in dendritic and T cells fully recapitulated this resistance. Mechanistically, this resistance was associated with a shift in the skin cytokine milieu toward a tumor nonpermissive microenvironment. Specifically, leukocytic Runx3 loss substantially increased the antitumorigenic cytokine thymic stromal lymphopoietin (TSLP) and profoundly decreased two protumorigenic cytokines, interleukin-17a and osteopontin. Therefore, inflammation-mediated tumor promotion requires leukocytic Runx3 expression, as its loss creates a unique cytokine composition that polarizes the tumor microenvironment to a potent antitumorigenic state.
authors: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.
authors: Omri
authors: O
authors: Bauer
authors: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.
authors: Shay
authors: S
authors: Hantisteanu
authors: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.
authors: Joseph
authors: J
authors: Lotem
authors: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel. Yoram.Groner@weizmann.ac.il.
authors: Yoram
authors: Y
authors: Groner
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D050677:Core Binding Factor Alpha 3 Subunit / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005434:Flow Cytometry; D015151:Immunoblotting; D007150:Immunohistochemistry; D007962:Leukocytes / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D011725:Pyridines / Q000633:toxicity; D012878:Skin Neoplasms / Q000139:chemically induced / Q000378:metabolism*
chemical_list: D002273:Carcinogens; D050677:Core Binding Factor Alpha 3 Subunit; D016207:Cytokines; D011725:Pyridines; C493730:Runx3 protein, mouse; C431843:tris(2-pyridylmethyl)amine; D015127:9,10-Dimethyl-1,2-benzanthracene