P110γ Deficiency Protects Against Pancreatic Carcinogenesis Yet Predisposes to Diet-Induced Hepatotoxicity
p110γ deficiency protects against pancreatic carcinogenesis yet predisposes to diet- induced hepatotoxicity Carolina Torresa,1, Georgina Mancinellia, Jose Cordoba-Chaconb, Navin Viswakarmac,d, Karla Castellanosa, Sam Grimaldoa, Sandeep Kumarc,d, Daniel Principed, Matthew J. Dormana, Ronald McKinneya, Emilio Hirsche, David Dawsonf,g, Hidayatullah G. Munshih, Ajay Ranac,d, and Paul J. Grippoa,1 aDepartment of Medicine, Division of Gastroenterology and Hepatology, University of Illinois at Chicago, Chicago, IL 60612; bDepartment of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Illinois at Chicago, Chicago, IL 60612; cResearch, Jesse Brown VA Medical Center, Chicago, IL 60612; dDepartment of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, IL 60612; eMolecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, Italy; fDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; gJonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; and hDepartment of Medicine, Northwestern University, Chicago, IL 60611 Edited by Ronald A. DePinho, University of Texas MD Anderson Cancer Center, Houston, TX, and approved May 23, 2019 (received for review August 1, 2018) Pancreatic ductal adenocarcinoma (PDAC) is notorious for its poor subunit. While the p110α and β are ubiquitously expressed, p110γ survival and resistance to conventional therapies. PI3K signaling is and δ are found predominantly in macrophages and leukocytes, al- implicated in both disease initiation and progression, and specific though an increasing number of studies show that p110γ is also inhibitors of selected PI3K p110 isoforms for managing solid tumors expressed to varying degrees in other cell types (11, 12), including are emerging.
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