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

	Temporal Dissection of K-ras(G12D) Mutant In Vitro and In Vivo Using a Regulatable K-ras(G12D) Mouse Allele
	Wang, ZY; Feng, Y; Bardessy, N; Wong, KK; Liu, XY; Ji, HB
刊名	PLOS ONE
	2012
卷号	7 期号:5 页码:e37308-e37308
通讯作者	Wang, ZY (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai, Peoples R China.,kwong1@partners.org ; xyliu@sibs.ac.cn ; hbji@sibs.ac.cn
英文摘要	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.
学科主题	Science & Technology - Other Topics
类目[WOS]	Multidisciplinary Sciences
关键词[WOS]	LUNG-CANCER PROGRESSION ; K-RAS ; INDUCED APOPTOSIS ; P53 RESTORATION ; ACTIVATION ; CELLS ; MICE ; MYC ; INHIBITORS ; EXPRESSION
收录类别	SCI
语种	英语
WOS记录号	WOS:000305338200070
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/588]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Wang, ZY,Feng, Y,Bardessy, N,et al. Temporal Dissection of K-ras(G12D) Mutant In Vitro and In Vivo Using a Regulatable K-ras(G12D) Mouse Allele[J]. PLOS ONE,2012,7(5):e37308-e37308.
APA	Wang, ZY,Feng, Y,Bardessy, N,Wong, KK,Liu, XY,&Ji, HB.(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-e37308.
MLA	Wang, ZY,et al."Temporal Dissection of K-ras(G12D) Mutant In Vitro and In Vivo Using a Regulatable K-ras(G12D) Mouse Allele".PLOS ONE 7.5(2012):e37308-e37308.