Ductal activation of oncogenic KRAS alone induces sarcomatoid phenotype

Yong Fu, Zobeida Cruz-Monserrate, H. Helen Lin, Yiyin Chung, Baoan Ji, Szu Min Lin, Steven Vonderfecht, Craig D. Logsdon, Chien Feng Li, David K. Ann

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6 Scopus citations

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.

Original languageEnglish (US)
Article number13347
JournalScientific reports
Volume5
DOIs
StatePublished - Aug 20 2015

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    Fu, Y., Cruz-Monserrate, Z., Helen Lin, H., Chung, Y., Ji, B., Lin, S. M., Vonderfecht, S., Logsdon, C. D., Li, C. F., & Ann, D. K. (2015). Ductal activation of oncogenic KRAS alone induces sarcomatoid phenotype. Scientific reports, 5, [13347]. https://doi.org/10.1038/srep13347