title: Human papilloma virus (HPV) E7-mediated attenuation of retinoblastoma (Rb) induces hPygopus2 expression via Elf-1 in cervical cancer.
abstract: The human papillomavirus (HPV) is the etiologic agent of cervical cancer. In this study, we provide evidence for the human Pygopus (hPygo)2 gene as a cellular biomarker for HPV-related disease. In a tumor microarray of cervical cancer progression, hPygo2 levels were greater in high-grade lesions and squamous cell carcinomas than in normal epithelia. Similarly, hPygo2 mRNA and protein levels were greater in HPV-positive cervical cancer cells relative to uninfected primary cells. RNA interference (RNAi)-mediated depletion of HPV-E7 increased whereas E74-like factor (Elf)-1 RNAi decreased association of Retinoblastoma (Rb) tumor suppressor with the hPygo2 promoter in cervical cancer cell lines. Transfection of dominant-active Rb inhibited Elf-1-dependent activation of hPygo2, whereas Elf-1 itself increased hPygo2 expression. Chromatin immunoprecipitation assays showed that Rb repressed hPygo2 by inhibiting Elf-1 at the Ets-binding site in the hPygo2 promoter. These results suggested that abrogation of Rb by E7 resulted in derepression of Elf-1, which in turn stimulated expression of hPygo2. Thus, initiation of hPygo2 expression by Elf-1 was required for proliferation of cervical cancer cells and its expression therefore may act as a surrogate marker for dysplasia.
authors.affiliation: Division of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philip Drive, St. John's, NL, Canada, A1B 3V6.
authors.forename: Youlian R
authors.initials: YR
authors.lastname: Tzenov
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Andrews
authors.forename: Kim
authors.initials: K
authors.lastname: Voisey
authors.forename: Paul
authors.initials: P
authors.lastname: Popadiuk
authors.forename: Jieying
authors.initials: J
authors.lastname: Xiong
authors.forename: Catherine
authors.initials: C
authors.lastname: Popadiuk
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Kao
mesh_terms: D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral / Q000235:genetics; D036383:Ephrin-A2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism; D052161:Human papillomavirus 18 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*
chemical_list: D036383:Ephrin-A2; D047908:Intracellular Signaling Peptides and Proteins; C453401:PYGO2 protein, human; D050725:Papillomavirus E7 Proteins; D016160:Retinoblastoma Protein