期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 103, 期 38, 页码 14152-14157出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0606698103
关键词
head and neck squamous cell carcinoma (HNSCC); human papillomavirus 16 (HPV16); minichromosome maintenance protein 7 (MCM7); p16; transgenic
资金
- NCI NIH HHS [CA022443, U19 CA113297, R01 CA098428, CA098428, P01 CA022443, CA113297] Funding Source: Medline
- NIDCR NIH HHS [R01 DE017315-03, DE017315, R01 DE017315-02, R01 DE017315-01, R01 DE017315] Funding Source: Medline
Head and neck squamous cell carcinoma (HNSCC) is a leading cause of cancer mortality worldwide. Recent reports have associated a subset of HNSCC with high-risk human papillomaviruses (HPVs), particularly HPV16, the same subset of HPVs responsible for the majority of cervical and anogenital cancers. In this study we describe a mouse model for HPV-associated HNSCC that employs mice transgenic for the HPV16 oncogenes E6 and E7. In these mice, E6 and E7 induce aberrant epithelial proliferation and, in the presence of a chemical carcinogen, they increase dramatically the animal's susceptibility to HNSCC. The cancers arising in the HPV16-transgenic mice mirror the molecular and histopathological characteristics of human HPV-positive HNSCC that distinguish the latter from human HPV-negative HNSCC, including overexpression of p16 protein and formation of more basaloid cancers. This validated model of HPV-associated HNSCC provides the means to define the contributions of individual HPV oncogenes to HNSCC and to understand the molecular basis for the differing clinical properties of HPV-positive and HPV-negative human HNSCC. From this study, we identify minichromosome maintenance protein 7 (MCM7) and p16 as potentially useful biomarkers for HPV-positive head and neck cancer.
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