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Deficiencies in the Fanconi anemia DNA damage response pathway increase sensitivity to HPV-associated head and neck cancer.

Publication ,  Journal Article
Park, JW; Pitot, HC; Strati, K; Spardy, N; Duensing, S; Grompe, M; Lambert, PF
Published in: Cancer Res
December 1, 2010

Patients with the rare genetic disease, Fanconi anemia (FA), are highly susceptible to squamous cell carcinomas arising at multiple anatomic sites including the head and neck region. Human papillomaviruses (HPVs), particularly HPV16, are associated with ∼20% of head and neck squamous cell carcinomas (HNSCCs) in the general population. Some but not other investigators have reported that HNSCCs in FA patients are much more frequently positive for HPV. In addition, studies have demonstrated an interaction between the HPV16 E7 oncoprotein and the FA pathway, a DNA damage response pathway deficient in FA patients. On the basis of these studies, it was hypothesized that the FA pathway contributes to repair of DNA damage induced by HPV16 E7, providing one explanation for why FA patients are predisposed to HPV-associated HNSCCs. To determine the importance of the FA pathway in modulating the oncogenic abilities of E7, we crossed K14E7 transgenic (K14E7) and fancD2 knockout mice (FancD2(-/-)) to establish K14E7/FancD2(-/-) and K14E7/FancD2(+/+) mice and monitored their susceptibility to HNSCC when treated with a chemical carcinogen. K14E7/FancD2(-/-) mice had a significantly higher incidence of HNSCC compared with K14E7/FancD2(+/+) mice. This difference correlated with an increased proliferative index and the increase in expression of biomarkers that are used to assess levels of DNA damage. These animal studies support the hypotheses that FA patients have increased susceptibility to HPV-associated cancer and that the FA DNA damage response pathway normally attenuates the oncogenic potential of HPV16 E7.

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Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

December 1, 2010

Volume

70

Issue

23

Start / End Page

9959 / 9968

Location

United States

Related Subject Headings

  • Signal Transduction
  • Quinolones
  • Papillomavirus E7 Proteins
  • Oncology & Carcinogenesis
  • Mice, Transgenic
  • Mice, Knockout
  • Mice, 129 Strain
  • Mice
  • Male
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
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Park, J. W., Pitot, H. C., Strati, K., Spardy, N., Duensing, S., Grompe, M., & Lambert, P. F. (2010). Deficiencies in the Fanconi anemia DNA damage response pathway increase sensitivity to HPV-associated head and neck cancer. Cancer Res, 70(23), 9959–9968. https://doi.org/10.1158/0008-5472.CAN-10-1291
Park, Jung Wook, Henry C. Pitot, Katerina Strati, Nicole Spardy, Stefan Duensing, Markus Grompe, and Paul F. Lambert. “Deficiencies in the Fanconi anemia DNA damage response pathway increase sensitivity to HPV-associated head and neck cancer.Cancer Res 70, no. 23 (December 1, 2010): 9959–68. https://doi.org/10.1158/0008-5472.CAN-10-1291.
Park JW, Pitot HC, Strati K, Spardy N, Duensing S, Grompe M, et al. Deficiencies in the Fanconi anemia DNA damage response pathway increase sensitivity to HPV-associated head and neck cancer. Cancer Res. 2010 Dec 1;70(23):9959–68.
Park, Jung Wook, et al. “Deficiencies in the Fanconi anemia DNA damage response pathway increase sensitivity to HPV-associated head and neck cancer.Cancer Res, vol. 70, no. 23, Dec. 2010, pp. 9959–68. Pubmed, doi:10.1158/0008-5472.CAN-10-1291.
Park JW, Pitot HC, Strati K, Spardy N, Duensing S, Grompe M, Lambert PF. Deficiencies in the Fanconi anemia DNA damage response pathway increase sensitivity to HPV-associated head and neck cancer. Cancer Res. 2010 Dec 1;70(23):9959–9968.

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

December 1, 2010

Volume

70

Issue

23

Start / End Page

9959 / 9968

Location

United States

Related Subject Headings

  • Signal Transduction
  • Quinolones
  • Papillomavirus E7 Proteins
  • Oncology & Carcinogenesis
  • Mice, Transgenic
  • Mice, Knockout
  • Mice, 129 Strain
  • Mice
  • Male
  • Humans