Human papillomavirus type 16 E6 and E7 oncoproteins act synergistically to cause head and neck cancer in mice.
High-risk human papillomaviruses (HPVs) contribute to cervical and other anogenital cancers, and they are also linked etiologically to a subset of head and neck squamous cell carcinomas (HNSCC). We previously established a model for HPV-associated HNSCC in which we treated transgenic mice expressing the papillomaviral oncoproteins with the chemical carcinogen 4-nitroquinoline-1-oxide (4-NQO). We found that the HPV-16 E7 oncoprotein was highly potent in causing HNSCC, and its dominance masked any potential oncogenic contribution of E6, a second papillomaviral oncoprotein commonly expressed in human cancers. In the current study, we shortened the duration of treatment with 4-NQO to reduce the incidence of cancers and discovered a striking synergy between E6 and E7 in causing HNSCC. Comparing the oncogenic properties of wild-type versus mutant E6 genes in this model for HNSCC uncovered a role for some but not other cellular targets of E6 previously shown to contribute to cervical cancer.
Jabbar
Sean
S
McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, 1400 University Avenue, Madison, WI 53706, USA.
Strati
Katerina
K
Shin
Myeong Kyun
MK
Pitot
Henry C
HC
Lambert
Paul F
PF
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology*; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D004195:Disease Models, Animal; D006258:Head and Neck Neoplasms / Q000139:chemically induced* / Q000821:virology*; D052162:Human papillomavirus 16 / Q000472:pathogenicity*; D051379:Mice; D008822:Mice, Transgenic; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D050725:Papillomavirus E7 Proteins / Q000502:physiology*; D030361:Papillomavirus Infections / Q000150:complications / Q000821:virology; D012097:Repressor Proteins / Q000502:physiology*; D037521:Virulence Factors / Q000502:physiology
D002273:Carcinogens; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D037521:Virulence Factors; C059731:oncogene protein E7, Human papillomavirus type 16; D015112:4-Nitroquinoline-1-oxide
EMBO J. 1991 Dec;10(13):4129-35
1661671
J Virol. 1999 Jul;73(7):5887-93
10364340
Arch Virol. 2008;153(3):397-408
18172569
J Virol. 2005 Sep;79(17):11392-402
16103190
J Biol Chem. 1998 Dec 18;273(51):34302-9
9852095
Oncogene. 2008 Nov 24;27(55):7018-30
19029942
Oncogene. 1999 Sep 30;18(40):5487-96
10523825
Proc Natl Acad Sci U S A. 1992 May 15;89(10):4442-6
1316608
Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):14152-7
16959885
Genes Dev. 2004 Sep 15;18(18):2269-82
15371341
J Gen Virol. 1998 Feb;79 ( Pt 2):371-4
9472622
Cancer Res. 2008 Apr 15;68(8):2622-31
18413729
Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2490-5
15699322
Science. 1995 Jul 28;269(5223):529-31
7624774
Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2290-5
9482878
Oncogene. 2000 Feb 10;19(6):719-25
10698489
J Natl Cancer Inst. 2009 Mar 18;101(6):412-23
19276448
Genes Dev. 1998 Jul 1;12(13):2061-72
9649509
Science. 2000 Jul 7;289(5476):113-6
10884224
Cell. 1993 Nov 5;75(3):495-505
8221889
Cancer Res. 2006 Oct 1;66(19):9393-400
17018593
Cancer Res. 2007 Dec 15;67(24):11585-93
18089787
J Virol. 1996 Mar;70(3):1873-81
8627712
Int J Cancer. 2003 Nov 10;107(3):394-400
14506739
J Biol Chem. 2004 Aug 20;279(34):35664-70
15175323
Oncogene. 2008 Mar 13;27(12):1800-4
17934525
Semin Oncol. 2004 Dec;31(6):744-54
15599852
Mol Cell Biol. 2000 Nov;20(21):8244-53
11027293
Dev Biol. 1974 Jul;39(1):23-36
4209528
Cancer Res. 2003 Aug 15;63(16):4862-71
12941807
Oncogene. 2009 Jan 8;28(1):1-8
18820705
Virology. 2002 Jan 20;292(2):309-20
11878933
Head Neck. 2008 Feb;30(2):139-47
17657785
Cancer Res. 2005 Sep 15;65(18):8266-73
16166303
Oncogene. 2001 Sep 6;20(39):5431-9
11571640
J Gen Virol. 1999 Jun;80 ( Pt 6):1513-1517
10374970
Cancer Res. 1996 Oct 15;56(20):4620-4
8840974
Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11612-6
9326658
J Natl Cancer Inst. 2000 May 3;92(9):709-20
10793107
J Virol. 2003 Jun;77(12):6957-64
12768014
J Biol Chem. 1998 May 29;273(22):13537-44
9593689
J Virol. 2002 Dec;76(24):13039-48
12438630
Science. 1989 Feb 17;243(4893):934-7
2537532
Cell. 1993 Sep 10;74(5):813-22
8374952
Mol Cell Biol. 2003 Dec;23(24):8970-81
14645510
Oncogene. 1998 Jan 8;16(1):43-52
9467941
Oncogene. 2002 Aug 29;21(38):5940-5
12185595
J Virol. 1999 Sep;73(9):7297-307
10438818
Cell. 1990 Dec 21;63(6):1129-36
2175676
Cancer. 2001 Aug 15;92(4):805-13
11550151
Science. 1978 Jun 30;200(4349):1448-59
96525
Oncogene. 2007 May 17;26(23):3321-8
17130828
J Biol Chem. 2001 Mar 23;276(12):9264-72
11104771
Oncogene. 2002 Feb 28;21(10):1510-7
11896579
Cancer Res. 2003 Mar 15;63(6):1188-91
12649174
Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8211-6
12821782
Oncogene. 2005 Sep 15;24(41):6222-30
16103886
Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4412-7
9114003
J Virol. 2007 Apr;81(8):4116-29
17267478
J Biol Chem. 2002 Jun 14;277(24):21730-9
11934887
Mol Cell Biol. 2003 Feb;23(4):1175-80
12556478
Virology. 2003 Dec 5;317(1):155-64
14675634
Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8058-63
9653139
Virology. 2000 Feb 15;267(2):141-50
10662610
Science. 1990 Apr 6;248(4951):76-9
2157286
Dev Biol. 1972 Jan;27(1):71-83
4621757
Biochem Biophys Res Commun. 1998 Aug 10;249(1):258-62
9705868
J Biol Chem. 2004 Jun 11;279(24):25729-44
15073179
Cancer Res. 2007 Feb 15;67(4):1626-35
17308103