Human papillomavirus type 16 E7 oncoprotein causes a delay in repair of DNA damage

Patients with human papillomavirus related (HPV+) head and neck cancers (HNCs) demonstrate improved clinical outcomes compared to traditional HPV negative (HPV−) HNC patients. We have recently shown that HPV+ HNC cells are more sensitive to radiation than HPV− HNC cells. However, roles of HPV oncoge...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	Radiotherapy and oncology Ročník 113; číslo 3; s. 337 - 344
Hlavní autoři:	Park, Jung Wook, Nickel, Kwangok P., Torres, Alexandra D., Lee, Denis, Lambert, Paul F., Kimple, Randall J.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Ireland Elsevier B.V 01.12.2014
Témata:	Animals Blotting, Western - methods Disease Models, Animal DNA Damage - genetics DNA damage repair DNA Repair - genetics Head and Neck Neoplasms - genetics Hematology, Oncology and Palliative Medicine HPV-positive head and neck cancer HPV16 E7 Humans Mice Mice, Transgenic Papillomaviridae - genetics Papillomavirus E7 Proteins - genetics Tumor Cells, Cultured HPV16 E7 DNA damage repair HPV-positive head and neck cancer
ISSN:	0167-8140, 1879-0887, 1879-0887
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	Patients with human papillomavirus related (HPV+) head and neck cancers (HNCs) demonstrate improved clinical outcomes compared to traditional HPV negative (HPV−) HNC patients. We have recently shown that HPV+ HNC cells are more sensitive to radiation than HPV− HNC cells. However, roles of HPV oncogenes in regulating the response of DNA damage repair remain unknown. Using immortalized normal oral epithelial cell lines, HPV+ HNC derived cell lines, and HPV16 E7-transgenic mice we assessed the repair of DNA damage using γ-H2AX foci, single and split dose clonogenic survival assays, and immunoblot. The ability of E7 to modulate expression of proteins associated with DNA repair pathways was assessed by immunoblot. HPV16 E7 increased retention of γ-H2AX nuclear foci and significantly decreased sublethal DNA damage repair. While phospho-ATM, phospho-ATR, Ku70, and Ku80 expressions were not altered by E7, Rad51 was induced by E7. Correspondingly, HPV+ HNC cell lines showed retention of Rad51 after γ-radiation. Our findings provide further understanding as to how HPV16 E7 manipulates cellular DNA damage responses that may underlie its oncogenic potential and influence the altered sensitivity to radiation seen in HPV+ HNC as compared to HPV− HNC.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0167-8140 1879-0887 1879-0887
DOI:	10.1016/j.radonc.2014.08.026