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T. Tran

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    P1.01 - Poster Session 1 - Cancer Biology (ID 143)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.01-018 - Epidermal growth factor up-regulates CD151 protein expression to promote non-small cell lung cancer proliferation (ID 1780)

      09:30 - 16:30  |  Author(s): T. Tran

      • Abstract

      CD151 is a member of the tetraspanin superfamily. It is expressed on the surface of a variety of cell types and is involved in cellular processes such as cell motility, adhesion, proliferation, differentiation and signal transduction. CD151 is a positive regulator of tumor progression; metastasis, tumor cell growth and survival. It is over-expressed in various cancers, including non-small cell lung cancers (NSCLCs). The 5-year survival rate for NSCLC patients with CD151 gene-positive tumors has been shown to be lower than that of those with CD151 gene-negative tumors. Most CD151 studies to date have compared the cellular functions in the presence or absence of CD151 via over-expression and knockdown techniques respectively. However, the endogenous mechanisms by which CD151 protein is up-regulated in cancer cells remain unknown. The epidermal growth factor (EGF) is a distinct ligand for EGF receptors (EGFRs). Over-expression of EGFRs has been observed in more than 60% of NSCLCs. EGF is secreted by NSCLCs, causing the hyperactivity of EGFRs and the activation of its downstream signaling pathways to promote cell proliferation. In this study, we investigated the impact of EGF stimulation on CD151 protein expression in NSCLC cell proliferation.

      A549 cells (a NSCLC cell line) were stimulated with increasing concentrations of EGF for 48hr and the CD151 protein abundance was measured via immunoblotting. To examine whether the effect of EGF on CD151 expression was a class-effect of growth factors, we also stimulated A549 cells with various stimulants (IL-1b, TNF-a, TGF-b1 and VEGF). To determine whether the effect of EGF on CD151 protein expression in NSCLC cells was cell-type selective, we examined the effects of EGF stimulation on CD151 protein abundance in other NSCLCs (H358, H1975), colon cancer (SW620) and breast cancer (MDA-MB-231) cell lines. Subsequently, silencing of CD151 via siRNA was carried out to investigate the effect of CD151 on EGF-stimulated A549 cell proliferation. Cell number was measured via trypan blue exclusion after 72hr of EGF stimulation, and phospho-ERK1/2 levels were examined via immunoblotting after 6hr of EGF stimulation.

      In A549 cells, EGF induced significant up-regulation of CD151 protein expression and this effect was not a class effect of growth factors. The up-regulation of CD151 protein by EGF was observed in more than one type of NSCLCs and in other cancer cell types. Silencing of CD151 down-regulated EGF-stimulated increase in A549 cell number and this effect was dependent on ERK1/2 phosphorylation.

      This is the first study to show that EGF up-regulates CD151 protein expression to promote NSCLC cell proliferation, possibly via the MAPK (ERK1/2) pathway.