國家衛生研究院 NHRI:Item 3990099045/5449

NHRI > National Institute of Environmental Health Sciences > Huei Lee(2009-2011) > Periodical Articles > Item 3990099045/5449

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/5449

Title:	A novel exon 15-deleted, splicing variant of slit2 shows potential for growth inhibition in addition to invasion inhibition in lung cancer
Authors:	Lin, YY;Yang, CH;Sheu, GT;Huang, CYF;Wu, YC;Chuang, SM;Fann, MJ;Chang, H;Lee, H;Chang, JT
Contributors:	Division of Environmental Health and Occupational Medicine
Abstract:	BACKGROUND: The axon guidance cue molecule Slit2 has been shown to suppress cancer cell invasion. However, the role of Slit2 in growth inhibition is still controversial. The authors identified a novel exon 15 (AKEQYFIP)-deleted slit2, located at the end of the second leucine-rich repeat (LRR2). Because LRR2 interacts with Robo1 receptor to inhibit invasion, they hypothesized that exon 15 plays an important role in modulating Slit2 function. +METHODS: Slit2 expression was assessed via microarray analysis in 27 lung adenocarcinomas. Exon 15-deleted slit2 (slit2-ΔE15) and exon 15-containing slit2 (slit2-WT) were cloned and expressed in the CL1-5 lung cancer cell line. The effect of exon 15 on Slit2-mediated cell growth was evaluated by a xenografted model and in vitro cell growth assays. The effect of exon 15 on Slit2-mediated invasion was analyzed with a modified Boyden chamber in vitro. +RESULTS: Tumor growth from CL1-5/Slit2-WT cells was comparable to that from CL1-5 cells bearing empty vector. However, tumor size from CL1-5/Slit2-ΔE15 cells was much smaller than that from Slit2-WT cells or vector control cells in the xenografted model. In vitro analyses demonstrated that Slit2-WT inhibits invasion of CL1-5 cells. In addition to inhibiting invasion, Slit2-ΔE15 greatly suppresses cell growth. +CONCLUSIONS: The data demonstrated that exon 15 modulates Slit2 function in growth inhibition of lung cancer cells. Because slit2-ΔE15 splice variant is present in low invasive cancer cells and nontumor lung tissues, loss of this splice variant is an important event in tumor progression and invasion. Cancer 2011.
Date:	2011-08
Relation:	Cancer. 2011 Aug;117(15):3404-3415.
Link to:	http://dx.doi.org/10.1002/cncr.25890
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-543X&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000293103800014
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=79960700661
Appears in Collections:	[Huei Lee(2009-2011)] Periodical Articles

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