title: Human papillomavirus-induced carcinogenesis with p53 deficiency in mouse: novel lymphomagenesis in HPV16E6E7 transgenic mice mimicking p53 defect.
abstract: To investigate the transforming activity of human papillomavirus (HPV) E6 and E7 genes in vivo, we previously established transgenic mouse lines containing HPV16E6E7, in which male mice develop a Leydig cell tumors with a very high incidence. Because HPV-induced carcinogenesis is highly related to p53, we changed the dose of p53 gene in the transgenic lines by the mice crossing with p53-disrupted mice. The transgenic mice with homozygous wild-type p53 alleles developed only the testicular tumor, whereas novel T cell lymphomagenesis occurred in the heterozygous p53-disrupted E6E7 (p53+/-E6E7) transgenic mice. In this tumor and even in the normal spleen, the absence of p53 protein was observed, whereas the p53 mRNA was expressed with a normal size, suggesting the degradation of p53 protein in these tissues. These results suggest that HPV16E6 could stimulate p53 protein degradation in mouse cells and induced the lymphomagenesis in a manner indistinguishable from p53 deficiency.
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Japan.
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: N
authors.initials: N
authors.lastname: Yoshioka
authors.forename: M
authors.initials: M
authors.lastname: Yutsudo
authors.forename: S
authors.initials: S
authors.lastname: Inafuku
authors.forename: K
authors.initials: K
authors.lastname: Aozasa
authors.forename: Y
authors.initials: Y
authors.lastname: Kitamura
authors.forename: S
authors.initials: S
authors.lastname: Aizawa
authors.forename: Y
authors.initials: Y
authors.lastname: Nishimune
authors.forename: A
authors.initials: A
authors.lastname: Hakura
authors.forename: G
authors.initials: G
authors.lastname: Kondoh
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D006801:Humans; D007984:Leydig Cell Tumor / Q000235:genetics / Q000473:pathology / Q000821:virology*; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000473:pathology / Q000821:virology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics / Q000472:pathogenicity*; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins / Q000235:genetics*; D013736:Testicular Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology*; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency*; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; C059731:oncogene protein E7, Human papillomavirus type 16