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@ARTICLE{Viarisio:130723,
author = {D. Viarisio$^*$ and K. Müller-Decker$^*$ and P. Zanna and
U. Kloz$^*$ and B. Aengeneyndt$^*$ and R. Accardi and C.
Flechtenmacher and L. Gissmann$^*$ and M. Tommasino},
title = {{N}ovel ß-{HPV}49 {T}ransgenic {M}ouse {M}odel of {U}pper
{D}igestive {T}ract {C}ancer.},
journal = {Cancer research},
volume = {76},
number = {14},
issn = {1538-7445},
address = {Philadelphia, Pa.},
publisher = {AACR},
reportid = {DKFZ-2017-05801},
pages = {4216 - 4225},
year = {2016},
abstract = {The beta genus of human papillomaviruses (ß-HPV) includes
approximately 50 different viral types that are subdivided
into five species (ß-1 through ß-5). Nonmelanoma cancers
may involve some ß-1 and ß-2 HPV types, but the biology of
most ß-HPV types and their possible connections to human
disease are still little characterized. In this study, we
studied the effects of ß-3 type HPV49 in a novel transgenic
(Tg) mouse model, using a cytokeratin K14 promoter to drive
expression of the E6 and E7 genes from this virus in the
basal skin epidermis and the mucosal epithelia of the
digestive tract (K14 HPV49 E6/E7-Tg mice). Viral oncogene
expression only marginally increased cellular proliferation
in the epidermis of Tg animals, compared with wild-type
littermates, and we observed no spontaneous tumor formation
during their entire lifespan. However, we found that K14
HPV49 E6/E7-Tg mice were highly susceptible to upper
digestive tract carcinogenesis upon initiation with
4-nitroquinoline 1-oxide (4NQO). This was a selective
effect, as the same mice did not exhibit any skin lesions
after chronic UV irradiation. Opposite results were observed
in an analogous Tg model expressing the ß-2 HPV38 E6 and E7
oncogenes at the same anatomic sites. While these mice were
highly susceptible to UV-induced skin carcinogenesis, as
previously shown, they were little affected by 4NQO
treatment. Overall, our findings highlight important
differences in the biologic properties of certain ß-type
HPV that affect their impact on carcinogenesis in an
anatomic site-specific manner. Cancer Res; 76(14); 4216-25.
©2016 AACR.},
keywords = {Oncogene Proteins, Viral (NLM Chemicals) / Papillomavirus
E7 Proteins (NLM Chemicals)},
cin = {F020 / W450 / W420},
ddc = {610},
cid = {I:(DE-He78)F020-20160331 / I:(DE-He78)W450-20160331 /
I:(DE-He78)W420-20160331},
pnm = {316 - Infections and cancer (POF3-316)},
pid = {G:(DE-HGF)POF3-316},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:27216183},
doi = {10.1158/0008-5472.CAN-16-0370},
url = {https://inrepo02.dkfz.de/record/130723},
}