A novel exon 15-deleted, splicing variant of Slit2 shows potential for growth inhibition in addition to invasion inhibition in lung cancer

Yu Ying Lin, Chun Hung Yang, Gwo Tarng Sheu, Chi Ying F Huang, Yu Chung Wu, Shu Ming Chuang, Ming Ji Fann, Han Chang, Huei Lee, Jinghua Tsai Chang

研究成果: 雜誌貢獻文章同行評審

7 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)3404-3415
頁數12
期刊Cancer
117
發行號15
DOIs
出版狀態已發佈 - 8月 1 2011
對外發佈

ASJC Scopus subject areas

  • 癌症研究
  • 腫瘤科

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