Temporal Dissection of K-ras\(^{G12D}\) Mutant In Vitro and In Vivo Using a Regulatable K-ras\(^{G12D}\) Mouse Allele

DSpace/Manakin Repository

Temporal Dissection of K-ras\(^{G12D}\) Mutant In Vitro and In Vivo Using a Regulatable K-ras\(^{G12D}\) Mouse Allele

Citable link to this page

 

 
Title: Temporal Dissection of K-ras\(^{G12D}\) Mutant In Vitro and In Vivo Using a Regulatable K-ras\(^{G12D}\) Mouse Allele
Author: Wang, Zuoyun; Bardessy, Nabeel; Liu, Xin-Yuan; Ji, Hongbin; Feng, Yan; Wong, Kwok-Kin

Note: Order does not necessarily reflect citation order of authors.

Citation: Wang, Zuoyun, Yan Feng, Nabeel Bardessy, Kwok-Kin Wong, Xin-Yuan Liu, and Hongbin Ji. 2012. Temporal dissection of K-ras\(^{G12D}\) mutant in vitro and in vivo using a regulatable K-ras\(^{G12D}\) mouse allele. PLoS ONE 7(5): e37308.
Full Text & Related Files:
Abstract: Animal models which allow the temporal regulation of gene activities are valuable for dissecting gene function in tumorigenesis. Here we have constructed a conditional inducible estrogen receptor-K-ras\(^{G12D}\) (ER-K-ras\(^{G12D}\)) knock-in mice allele that allows us to temporally switch on or off the activity of K-ras oncogenic mutant through tamoxifen administration. In vitro studies using mice embryonic fibroblast (MEF) showed that a dose of tamoxifen at 0.05 \(\mu\)M works optimally for activation of ER-K-ras\(^{G12D}\) independent of the gender status. Furthermore, tamoxifen-inducible activation of K-ras\(^{G12D}\) promotes cell proliferation, anchor-independent growth, transformation as well as invasion, potentially via activation of downstream MAPK pathway and cell cycle progression. Continuous activation of K-ras\(^{G12D}\) in vivo by tamoxifen treatment is sufficient to drive the neoplastic transformation of normal lung epithelial cells in mice. Tamoxifen withdrawal after the tumor formation results in apoptosis and tumor regression in mouse lungs. Taken together, these data have convincingly demonstrated that K-ras mutant is essential for neoplastic transformation and this animal model may provide an ideal platform for further detailed characterization of the role of K-ras oncogenic mutant during different stages of lung tumorigenesis.
Published Version: doi:10.1371/journal.pone.0037308
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350485/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10381373
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters