@article{3140d42231374e5bb05d34677ae45b88,
title = "Ductal activation of oncogenic KRAS alone induces sarcomatoid phenotype",
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.",
author = "Yong Fu and Zobeida Cruz-Monserrate and {Helen Lin}, H. and Yiyin Chung and Baoan Ji and Lin, {Szu Min} and Steven Vonderfecht and Logsdon, {Craig D.} and Li, {Chien Feng} and Ann, {David K.}",
note = "Funding Information: We would like to thank Drs. Xiwei Wu and Jinhui Wang and Mr. Charles Warden of DNA-sequencing core for RNA-sequencing data analyses, members of Dr. Ann{\textquoteright}s laboratory for helpful discussions, Kelly Sprague for technical help and Yan Liu for help with animal genotyping at MDACC, Dr. Hong-Lin Ho (E-Da Hospital, Kaohsiung, Taiwan), Dr. Jui Lan (Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan), and Dr. Peir-In Liang (Kaohsiung Medical University Hospital, Kaohsiung, Taiwan) for providing clinicopathological information. This research was supported in part by funds from The Lockton Endowment (to C.D.L.), National Institute of Diabetes and Digestive and Kidney Diseases Diversity Supplement DK052067-08 (to C.D.L. for Z.C.-M.), the MDACC CCSG CA16672 (to C.D.L.), the Ministry of Science and Technology of Taiwan 101-2320-B-384-001-MY3 (to C.F.L.) and R01DE10742, R21DE023298 (to D.K.A.).",
year = "2015",
month = aug,
day = "20",
doi = "10.1038/srep13347",
language = "English (US)",
volume = "5",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}