Bovine papillomavirus genome elicits skin tumours in transgenic mice

Abstract

Transmission of the bovine papillomavirus-1 (BPV-1) genome through the mouse germ line results in the heritable formation of fibropapillomas of the skin, a tissue-specific phenotype analogous to that observed in natural BPV-1 infection of cattle. Oncogenesis is slow, with tumours first arising at 8-9 months of age, usually in areas prone to wounding. Extrachromosomal BPV-1 DNA is detected in all tumours, whereas normal tissues show only integrated DNA.

Transcription factors junB and c-jun are selectively up-regulated and functionally implicated in fibrosarcoma development.

“…The epidermal layer in aggressive fibromatosis lesions is enlarged and shows a significant increase in JunB and c-Jun. As described earlier, some of the lesions in BPV-1 mice have an atypical epidermis, which does not progress to neoplasia and is inferred to be reactive to the dermal proliferation (Lacey et al 1986). Secondary antibody controls indicate that the cytoplasmic staining is nonspecific.…”

“…Generation of BPV1.69 and BPV.69rI transgenic mice and their tumor phenotype has been described previously (Lacey et al 1986;Lindgren et al 1989).…”

“…In one transgenic mouse model of this process, mice harboring the bovine papillomavirus type 1 (BPV-1) genome develop dermal fibrosarcomas in a pathway comprised of at least three stages (Lacey et al 1986). Initially, two histological grades of hyperplasia arise: mild fibromatosis and aggressive fibromatosis.…”

Glucocorticoids Inhibit Apoptosis during Fibrosarcoma Development by Transcriptionally Activating Bcl-xL

“…As negative control the primers 5Ј-TGGGCTGGCTCCCTGGTCAG-3Ј and 5Ј-CCTCGGTCACG-GATCTTAGGC-3Ј, which amplify a 112-bp fragment corresponding to murine Bak sequence Ϫ960 to Ϫ848 (GenBank TM accession number Y 13232), were included in the same PCR reactions. (27) and in cultured cells (21), and it is inhibited by dexamethasone, a GR agonist (53). We examined the effects of glucocorticoids on cell death during fibrosarcoma progression.…”

Abnormalities of epidermal differentiation associated with expression of the human papillomavirus type 1 early region in transgenic mice

“…In the first such study, the entire genome of a bovine papillomavirus (BPV-1, which induces fibropapillomas in cattle) was introduced into the mouse genome (Lacey et al, 1986). Transgenic mice in this line initially appeared normal, but later developed patches of abnormal skin and protuberant tumours at sites of epithelial wounding.…”