Abstract |
The prognosis of head-and-neck squamous cell carcinoma ( HNSCC) has not been improved in the past 20 years. Validation of HNSCC biomarkers for targeted therapy has been hindered by a lack of animal models mimicking human HNSCC at both the pathological and molecular levels. Here we report that overexpression of K-ras or H-ras and loss of transforming growth factor-beta type II receptor (TGFbetaRII) are common events in human HNSCC. Activation of either K-ras or H-ras in combination with TGFbetaRII deletion from mouse head-and-neck epithelia caused HNSCC with complete penetrance, some of which progressed to metastases. These tumors displayed pathology indistinguishable from human HNSCCs and exhibited multiple molecular alterations commonly found in human HNSCCs. Additionally, elevated endogenous TGFbeta1 in these lesions contributed to inflammation and angiogenesis. Our data suggest that targeting common oncogenic pathways in tumor epithelia together with blocking the effect of TGFbeta1 on tumor stroma may provide a novel therapeutic strategy for HNSCC.
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Authors | Shi-Long Lu, Heather Herrington, Douglas Reh, Stephen Weber, Sophia Bornstein, Donna Wang, Allen G Li, Chin-Fang Tang, Yasmin Siddiqui, Jo Nord, Peter Andersen, Christopher L Corless, Xiao-Jing Wang |
Journal | Genes & development
(Genes Dev)
Vol. 20
Issue 10
Pg. 1331-42
(May 15 2006)
ISSN: 0890-9369 [Print] United States |
PMID | 16702406
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Receptors, Transforming Growth Factor beta
- Protein Serine-Threonine Kinases
- Receptor, Transforming Growth Factor-beta Type II
- Proto-Oncogene Proteins p21(ras)
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Topics |
- Animals
- Carcinoma, Squamous Cell
(blood supply, genetics, secondary)
- Gene Deletion
- Humans
- Mice
- Mice, Mutant Strains
- Mouth Neoplasms
(blood supply, genetics, pathology)
- Mutation
- Neovascularization, Pathologic
(genetics, pathology)
- Protein Serine-Threonine Kinases
- Proto-Oncogene Proteins p21(ras)
(genetics, metabolism)
- Receptor, Transforming Growth Factor-beta Type II
- Receptors, Transforming Growth Factor beta
(genetics)
- Transcriptional Activation
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