title: Functional activation of PPARγ in human upper aerodigestive cancer cell lines.
abstract: Upper aerodigestive cancer is an aggressive malignancy with relatively stagnant long-term survival rates over 20 yr. Recent studies have demonstrated that exploitation of PPARγ pathways may be a novel therapy for cancer and its prevention. We tested whether PPARγ is expressed and inducible in aerodigestive carcinoma cells and whether it is present in human upper aerodigestive tumors. Human oral cancer CA-9-22 and NA cell lines were treated with the PPAR activators eicosatetraynoic acid (ETYA), 15-deoxy-δ- 12,14-prostaglandin J2 (PG-J2), and the thiazolidinedione, ciglitazone, and evaluated for their ability to functionally activate PPARγ luciferase reporter gene constructs. Cellular proliferation and clonogenic potential after PPARγ ligand treatment were also evaluated. Aerodigestive cancer specimens and normal tissues were evaluated for PPARγ expression on gene expression profiling and immunoblotting. Functional activation of PPARγ reporter gene constructs and increases in PPARγ protein were confirmed in the nuclear compartment after PPARγ ligand treatment. Significant decreases in cell proliferation and clonogenic potential resulted from treatment. Lipid accumulation was induced by PPARγ activator treatment. 75% of tumor specimens and 100% of normal control tissues expressed PPARγ RNA, and PPARγ protein was confirmed in 66% of tumor specimens analyzed by immunoblotting. We conclude PPARγ can be functionally activated in upper aerodigestive cancer and that its activation downregulates several features of the neoplastic phenotype. PPARγ expression in human upper aerodigestive tract tumors and normal cells potentially legitimizes it as a novel intervention target in this disease. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Simon K
authors.initials: SK
authors.lastname: Wright
authors.affiliation: Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Beverly R
authors.initials: BR
authors.lastname: Wuertz
authors.affiliation: Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota.
authors.forename: George
authors.initials: G
authors.lastname: Harris
authors.affiliation: Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Raed
authors.initials: R
authors.lastname: Abu Ghazallah
authors.affiliation: Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Miller
authors.affiliation: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Gaffney
authors.affiliation: Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Frank G
authors.initials: FG
authors.lastname: Ondrey
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D009055:Mouth / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D047495:PPAR gamma / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001095:Arachidonic Acids; D047495:PPAR gamma; D045162:Thiazolidinediones; C037112:9-deoxy-delta-9-prostaglandin D2; C089946:2,4-thiazolidinedione; D015230:Prostaglandin D2; C039671:ciglitazone
keywords: genomic; oral cancer; prostaglandin; thiazolidinedione; transdifferentiation