Thymic hyperplasia and lung carcinomas in a line of mice transgenic for keratin 5-driven HPV16 E6/E7 oncogenes.
Human Papillomavirus type 16 (HPV-16) is the cause of both benign lesions and ano-genital cancers. In HPV-associated cancers the transforming properties of the expressed viral E6 and E7 proteins have been revealed by a number of different assays. We have generated transgenic mice expressing HPV-16 E6/E7 genes under the control of the murine keratin 5 gene promoter, which should confer cell-type specific expression in the basal cells of squamous stratified epithelia. Transgenic mice developed thymic hyperplasia and lung neoplasia with 100% frequency, the thymus showing a size increase at 2 months and reaching the maximum dimension at 6 months, when lung carcinomas appeared. After this time the size of hyperplastic thymi decreased, while malignant formations invaded the mediastinal area. Hepatic metastasis could be also observed in some of the animals at the autopsy and death invariably occurred around 10-11 months of age.
Carraresi
L
L
Department of Physiopathology and Experimental Medicine, University of Siena, Via Aldo Moro, 53100 Siena, Italy.
Tripodi
S A
SA
Mulder
L C
LC
Bertini
S
S
Nuti
S
S
Schuerfeld
K
K
Cintorino
M
M
Bensi
G
G
Rossini
M
M
Mora
M
M
D000818:Animals; D002277:Carcinoma / Q000150:complications / Q000473:pathology / Q000821:virology*; D053569:Keratin-15; D053555:Keratin-5; D007633:Keratins / Q000235:genetics*; D008113:Liver Neoplasms / Q000150:complications / Q000473:pathology / Q000556:secondary; D008175:Lung Neoplasms / Q000150:complications / Q000473:pathology / Q000821:virology*; D051379:Mice; D008822:Mice, Transgenic; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000494:pharmacology*; D009929:Organ Size; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000150:complications / Q000473:pathology*; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012097:Repressor Proteins; D013950:Thymus Gland / Q000473:pathology; D013952:Thymus Hyperplasia / Q000150:complications / Q000473:pathology / Q000821:virology*; D014412:Tumor Virus Infections / Q000150:complications / Q000473:pathology*
C068651:E6 protein, Human papillomavirus type 16; C503940:KRT5 protein, human; D053569:Keratin-15; D053555:Keratin-5; C492053:Krt15 protein, mouse; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D007633:Keratins