Details

Autor(en) / Beteiligte

• Liu, Xiqiang
• Jiang, Lu
• Shi, Fei
• Zhou, Xiaofeng

Titel

Abstract 2566: Mesenchymal to epithelial transition associates with drug resistance in tongue squamous cell carcinoma cell line

Ist Teil von

• Cancer research (Chicago, Ill.), 2010-04, Vol.70 (8_Supplement), p.2566-2566

Erscheinungsjahr

2010

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Abstract Epithelial to mesenchymal transition (EMT) has been implicated in altered drug sensitivity to various chemotherapeutic agents. Herein, we investigate whether this phenomenon would play a role in acquired resistance to cisplatin. We firstly established a cisplatin-resistant subline (UMcis, IC50 = 19.8 µM), which was derived from the cisplatin-sensitive tongue squamous cell carcinoma cell line, UM1 (IC50 = 3.6 µM). The UMcis cells showed cross-resistance against other chemotherapeutic drugs with divergent mechanisms of action [5-fluoro-uracil (5-FU), paclitaxel and epidermal growth factor receptor-tyrosine kinase inhibitor erlotinib]. Genome-wide expressional profiling was performed on the paired cell lines. Interestingly, a large number of genes associated with EMT (or reversed EMT, MET) were differentially expressed between the two cell lines. We confirmed that increased expression of E-Cadherin combined with the loss of Vimentin, Slug, Twist1 and MMP2 by immunoblotting was associated with drug resistance. Importantly, downregulation of E-Cadherin in UMcis cells not only increased the expression of mesenchymal markers, such as Vimentin, Slug and Twist1, but also restored drug sensitivity. Moreover, concurrent treatment with transforming growth factor-beta 1 and epidermal growth factor induced EMT in the UMcis cells, which also led to altered chemo-responsiveness. Therefore, our results suggest that induction of MET may contribute to the decreased efficiency of cisplatin-based chemotherapy and acquired drug resistance in tongue cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2566.