1. Ductal activation of oncogenic KRAS alone induces sarcomatoid phenotype.
- Author
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Fu Y, Cruz-Monserrate Z, Helen Lin H, Chung Y, Ji B, Lin SM, Vonderfecht S, Logsdon CD, Li CF, and Ann DK
- Subjects
- Adult, Aged, Aged, 80 and over, Cell Proliferation, Cetuximab pharmacology, Drug Resistance, Neoplasm drug effects, ErbB Receptors genetics, Female, Humans, Male, Middle Aged, Mutation genetics, Phenotype, Signal Transduction drug effects, Submandibular Gland pathology, Proto-Oncogene Proteins p21(ras) genetics, Salivary Ducts pathology, Salivary Gland Neoplasms genetics, Salivary Gland Neoplasms pathology, Sarcoma genetics, Sarcoma pathology
- Abstract
Salivary duct carcinoma (SDC) is an uncommon, but aggressive malignant tumor with a high mortality rate. Herein, we reported the detection of somatic KRAS A146T and Q61H mutations in 2 out of 4 (50%) sarcomatoid SDC variants. Transgenic mice carrying the human oncogenic KRAS(G12V), which spatiotemporal activation by tamoxifen (TAM)-inducible Cre recombinase Ela-CreERT in the submandibular gland (SMG) ductal cells, was established and characterized. Visible carcinoma was detected as early as day-15 following oncogenic KRAS(G12V) induction alone, and these tumors proliferate rapidly with a median survival of 28-days accompanied with histological reminiscences to human sarcomatoid SDC variants. Moreover, these tumors were resistant to cetuximab treatment despite augmented EGFR signaling, attesting its malignancy. Our findings suggest that LGL-KRas(G12V);Ela-CreERT transgenic mice could serve as a useful preclinical model for investigating underlying mechanisms and developing potential therapies.
- Published
- 2015
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