Ductal activation of oncogenic KRAS alone induces sarcomatoid phenotype

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

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

Fingerprint

Salivary Ducts
Carcinoma
Phenotype
Transgenic Mice
Neoplasms
Submandibular Gland
Tamoxifen
Mutation
Survival
Mortality
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

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

Ductal activation of oncogenic KRAS alone induces sarcomatoid phenotype. / Fu, Yong; Cruz-Monserrate, Zobeida; Helen Lin, H.; Chung, Yiyin; Ji, Baoan D; Lin, Szu Min; Vonderfecht, Steven; Logsdon, Craig D.; Li, Chien Feng; Ann, David K.

In: Scientific Reports, Vol. 5, 13347, 20.08.2015.

Research output: Contribution to journalArticle

Fu, Y, Cruz-Monserrate, Z, Helen Lin, H, Chung, Y, Ji, BD, Lin, SM, Vonderfecht, S, Logsdon, CD, Li, CF & Ann, DK 2015, 'Ductal activation of oncogenic KRAS alone induces sarcomatoid phenotype', Scientific Reports, vol. 5, 13347. https://doi.org/10.1038/srep13347
Fu Y, Cruz-Monserrate Z, Helen Lin H, Chung Y, Ji BD, Lin SM et al. Ductal activation of oncogenic KRAS alone induces sarcomatoid phenotype. Scientific Reports. 2015 Aug 20;5. 13347. https://doi.org/10.1038/srep13347
Fu, Yong ; Cruz-Monserrate, Zobeida ; Helen Lin, H. ; Chung, Yiyin ; Ji, Baoan D ; Lin, Szu Min ; Vonderfecht, Steven ; Logsdon, Craig D. ; Li, Chien Feng ; Ann, David K. / Ductal activation of oncogenic KRAS alone induces sarcomatoid phenotype. In: Scientific Reports. 2015 ; Vol. 5.
@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 Ji, {Baoan D} and Lin, {Szu Min} and Steven Vonderfecht and Logsdon, {Craig D.} and Li, {Chien Feng} and Ann, {David K.}",
year = "2015",
month = "8",
day = "20",
doi = "10.1038/srep13347",
language = "English (US)",
volume = "5",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Ductal activation of oncogenic KRAS alone induces sarcomatoid phenotype

AU - Fu, Yong

AU - Cruz-Monserrate, Zobeida

AU - Helen Lin, H.

AU - Chung, Yiyin

AU - Ji, Baoan D

AU - Lin, Szu Min

AU - Vonderfecht, Steven

AU - Logsdon, Craig D.

AU - Li, Chien Feng

AU - Ann, David K.

PY - 2015/8/20

Y1 - 2015/8/20

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84939622678&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84939622678&partnerID=8YFLogxK

U2 - 10.1038/srep13347

DO - 10.1038/srep13347

M3 - Article

C2 - 26289340

AN - SCOPUS:84939622678

VL - 5

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 13347

ER -