title: A truncated human Ah receptor suppresses growth of human cervical tumor xenografts by interfering with hypoxia signaling.
abstract: We used a xenograft model to investigate whether the aryl hydrocarbon receptor deletion construct CDelta553 suppresses tumor growth. HeLa cells that were infected with CDelta553 expressing adenovirus (Ad553) formed very small tumors whereas the control adenovirus-infected cells formed large tumors at day 15. CDelta553 inhibited the formation of the HIF-1 DNA complex and suppressed the induction of the HIF-1alpha target proteins CAIX and GLUT1. The Ad553 tumors had less HIF-1 function since they showed reduced microvessel formation and lesser amounts of HIF-1alpha, Arnt, phospho-Akt, CAIX, and GLUT1. Proteasome-mediated Arnt degradation was enhanced in Ad553-infected HeLa cells and tumors.
authors.affiliation: Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA 95211, United States.
authors.forename: Depeng
authors.initials: D
authors.lastname: Wang
authors.forename: Jesika S
authors.initials: JS
authors.lastname: Faridi
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Li
authors.forename: William K
authors.initials: WK
authors.lastname: Chan
mesh_terms: D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D006367:HeLa Cells; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy*; D050505:Mutant Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D009368:Neoplasm Transplantation; D015202:Protein Engineering / Q000379:methods; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D017384:Sequence Deletion; D015398:Signal Transduction / Q000187:drug effects*; D014162:Transfection; D014183:Transplantation, Heterologous; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: C497396:ARNT protein, human; D050505:Mutant Proteins; D018336:Receptors, Aryl Hydrocarbon; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator
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