| Summary: | 碩士 === 中山醫學大學 === 醫學研究所 === 100 === Slit2 is a secreted protein. Previous studies have shown that Slit2 plays a tumor suppressor role in many cancers. Our laboratory identified two splicing variants of slit2, slit2-WT and slit2 ΔE15, Slit2-WT has ability to inhibit cancer cell invasion, while Slit2-ΔE15 possess not only invasion inhibition but also growth inihibition capability in CL1-5 lung cancer cells. When we deleted EGF6/LamG domains of Slit2-ΔE15, Slit2-ΔE15-ΔEGF6/LamG, the ability of growth and invasion inhibition was abolished. This result suggested that the EGF6/LamG domain is required for Slit2-ΔE15-mediated growth and invasion inhibition. In this study, we further deleted EGF6/LamG domain in Slit2-WT, Slit2-WT-ΔEGF6/LamG, to elucidate if EGF6/LamG region affects the ability of Slit2-WT to inhibit cell invasion. Resuts showed that Slit2-WT-ΔEGF6/LamG still inhibited cancer cells invasion, but surprisingly, it gains growth inhibitory capability. Our previous studies also found that the ratio of Slit2-ΔE15 to Slit2-WT expression in normal counterpart of lung cancer pecimen was extremely low. However, in 54 pneumothorax patients’ lung tissues, 40.7% of the lung tissue expressed Slit2-ΔE15 levels equal to or higher than the Slit2-WT. Among them, 12.9% of the samples even expressed slit2-ΔE15 only. We next examined slit2 splicing forms expression in murine brain and lung tissues. Results showed that most of the murine brain and lung expressed either form of slit2. Brain tissues expressed slit2-WT form except for one brain which expressed both slit2-WT and slit2-ΔE15 forms; lung tissues expressed slit2-ΔE15 form more than slit2-WT. These results suggested that Slit2 splicing variants may be regulated by tissue-specific splicing factors. We hypothesized that during lung tumorigenesis, the expression of Slit2 in the tumor microenvironment switch from Slit2-ΔE15 form to Slit2-WT form thus relief growth inhibition of cancer cells.
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