PMID- 21779166
OWN - NLM
STAT- MEDLINE
DCOM- 20111114
LR  - 20211020
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 7
IP  - 7
DP  - 2011 Jul
TI  - E6 and E7 from beta HPV38 cooperate with ultraviolet light in the development of 
      actinic keratosis-like lesions and squamous cell carcinoma in mice.
PG  - e1002125
LID - 10.1371/journal.ppat.1002125 [doi]
LID - e1002125
AB  - Cutaneous beta human papillomavirus (HPV) types appear to be involved in the 
      development of non-melanoma skin cancer (NMSC); however, it is not entirely clear 
      whether they play a direct role. We have previously shown that E6 and E7 
      oncoproteins from the beta HPV type 38 display transforming activities in several 
      experimental models. To evaluate the possible contribution of HPV38 in a 
      proliferative tissue compartment during carcinogenesis, we generated a new 
      transgenic mouse model (Tg) where HPV38 E6 and E7 are expressed in the 
      undifferentiated basal layer of epithelia under the control of the Keratin 14 
      (K14) promoter. Viral oncogene expression led to increased cellular proliferation 
      in the epidermis of the Tg animals in comparison to the wild-type littermates. 
      Although no spontaneous formation of tumours was observed during the lifespan of 
      the K14 HPV38 E6/E7-Tg mice, they were highly susceptible to 
      7,12-dimethylbenz(a)anthracene (DMBA)/12-0-tetradecanoylphorbol-13-acetate (TPA) 
      two-stage chemical carcinogenesis. In addition, when animals were exposed to 
      ultraviolet light (UV) irradiation, we observed that accumulation of p21(WAF1) 
      and cell-cycle arrest were significantly alleviated in the skin of Tg mice as 
      compared to wild-type controls. Most importantly, chronic UV irradiation of Tg 
      mice induced the development of actinic keratosis-like lesions, which are 
      considered in humans as precursors of squamous cell carcinomas (SCC), and 
      subsequently of SCC in a significant proportion of the animals. In contrast, 
      wild-type animals subjected to identical treatments did not develop any type of 
      skin lesions. Thus, the oncoproteins E6 and E7 from beta HPV38 significantly 
      contribute to SCC development in the skin rendering keratinocytes more 
      susceptible to UV-induced carcinogenesis.
FAU - Viarisio, Daniele
AU  - Viarisio D
AD  - DKFZ, Heidelberg, Germany.
FAU - Mueller-Decker, Karin
AU  - Mueller-Decker K
FAU - Kloz, Ulrich
AU  - Kloz U
FAU - Aengeneyndt, Birgit
AU  - Aengeneyndt B
FAU - Kopp-Schneider, Annette
AU  - Kopp-Schneider A
FAU - Grone, Hermann-Josef
AU  - Grone HJ
FAU - Gheit, Tarik
AU  - Gheit T
FAU - Flechtenmacher, Christa
AU  - Flechtenmacher C
FAU - Gissmann, Lutz
AU  - Gissmann L
FAU - Tommasino, Massimo
AU  - Tommasino M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110714
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 (Carcinogens)
RN  - 0 (Cdkn1a protein, mouse)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Oncogene Proteins, Viral)
RN  - 57-97-6 (9,10-Dimethyl-1,2-benzanthracene)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
EIN - PLoS Pathog. 2016 Oct 28;12 (10 ):e1006005. PMID: 27792794
MH  - 9,10-Dimethyl-1,2-benzanthracene/adverse effects/pharmacology
MH  - Alphapapillomavirus
MH  - Animals
MH  - Carcinogens/pharmacology
MH  - Carcinoma, Squamous Cell/etiology/genetics/*metabolism/pathology/virology
MH  - Cyclin-Dependent Kinase Inhibitor p21/genetics/metabolism
MH  - Epidermis/metabolism/pathology/virology
MH  - Humans
MH  - Keratinocytes/metabolism/pathology/virology
MH  - Keratosis, Actinic/genetics/*metabolism/pathology/virology
MH  - Mice
MH  - Mice, Transgenic
MH  - Oncogene Proteins, Viral/*biosynthesis/genetics
MH  - Papillomavirus Infections/genetics/*metabolism/pathology
MH  - Skin Neoplasms/etiology/genetics/*metabolism/pathology/virology
MH  - Tetradecanoylphorbol Acetate/adverse effects/pharmacology
MH  - Ultraviolet Rays/*adverse effects
PMC - PMC3136451
COIS- The authors have declared that no competing interests exist.
EDAT- 2011/07/23 06:00
MHDA- 2011/11/15 06:00
PMCR- 2011/07/14
CRDT- 2011/07/23 06:00
PHST- 2011/01/10 00:00 [received]
PHST- 2011/05/03 00:00 [accepted]
PHST- 2011/07/23 06:00 [entrez]
PHST- 2011/07/23 06:00 [pubmed]
PHST- 2011/11/15 06:00 [medline]
PHST- 2011/07/14 00:00 [pmc-release]
AID - PPATHOGENS-D-11-00073 [pii]
AID - 10.1371/journal.ppat.1002125 [doi]
PST - ppublish
SO  - PLoS Pathog. 2011 Jul;7(7):e1002125. doi: 10.1371/journal.ppat.1002125. Epub 2011 
      Jul 14.