Journal
JOURNAL OF VIROLOGY
Volume 81, Issue 23, Pages 13265-13270Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.01121-07
Keywords
-
Categories
Funding
- NCI NIH HHS [P01 CA022443-290006, R01 CA112598-03, R01 CA098428-06, P01 CA022443-300006, P01 CA022443-280006, R01 CA098428-07, P01 CA022443, P01 CA022443-310006, R01 CA112598, R01 CA098428, R01 CA022443] Funding Source: Medline
- NIDCR NIH HHS [R01 DE017315-03, R01 DE017315, R01 DE017315-04] Funding Source: Medline
Ask authors/readers for more resources
Fanconi anemia (FA) patients have an increased risk for squamous cell carcinomas (SCCs) at sites of predilection for infection with high-risk human papillomavirus (HPV) types, including the oral cavity and the anogenital tract. We show here that activation of the FA pathway is a frequent event in cervical SCCs. We found that FA pathway activation is triggered mainly by the HPV type 16 (HPV-16) E7 oncoprotein and is associated with an enhanced formation of large FANCD2 foci and recruitment of FANCD2 as well as FANCD1/BRCA2 to chromatin. Episomal expression of HPV-16 oncoproteins was sufficient to activate the FA pathway. Importantly, the expression of HPV-16 E7 in FA-deficient cells led to accelerated chromosomal instability. Taken together, our findings establish the FA pathway as an early host cell response to high-risk HPV infection and may help to explain the greatly enhanced susceptibility of FA patients to squamous cell carcinogenesis at anatomic sites that are frequently infected by high-risk HPVs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available