title: Expression of Pirh2, a newly identified ubiquitin protein ligase, in lung cancer.
abstract: Maintenance of p53 function is important for normal cell growth and development, and loss of p53 function contributes directly to malignant tumor development. The recently discovered Pirh2 protein is an ubiquitin-protein ligase that negatively regulates p53 through activity by targeting it for degradation. To determine how Pirh2 may mediate lung tumorigenesis, we evaluated Pirh2 expression in human and mouse lung tumor samples and paired normal lung tissues using immunoblot analysis and immunohistochemistry. Pirh2 protein expression was higher in 27 (84%) of 32 human lung neoplasms than in matched normal lung tissue and in 14 of 15 mouse lung tumors evaluated. In addition, p53 protein was more ubiquitinated in the mouse lung tumors than in normal tissue, and overall p53 expression was lower than that in normal tissue. These results are consistent with the hypothesis that increased Pirh2 expression affects lung tumorigenesis by reducing p53 activity. To our knowledge, this is the first description of altered Pirh2 expression in human and mouse tumors.
authors.affiliation: Comprehensive Cancer Center and Department of Internal Medicine, The Ohio State University College of Medicine and Public Health, Columbus 43210-1240, USA.
authors.forename: Wenrui
authors.initials: W
authors.lastname: Duan
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Druhan
authors.forename: Wei-Guo
authors.initials: WG
authors.lastname: Zhu
authors.forename: Carl
authors.initials: C
authors.lastname: Morrison
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Otterson
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Villalona-Calero
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008168:Lung / Q000737:chemistry; D008175:Lung Neoplasms / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000032:analysis* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; C485369:RCHY1 protein, human; D044767:Ubiquitin-Protein Ligases