Expression of FLI-1 and the proliferation and survival of small cell lung cancer cells.

Abstract

e18550 Background: Small cell lung cancer (SCLC) exhibits aggressive behavior, rapid growth, early spread to distant sites. Over the last few decades, prognosis for patients with SCLC has changed little and there remains an critical need for evaluating novel agents. Here, we report that Fli-1 (Friend leukemia virus integration 1), a transcription factor and member of the Ets family, has an essential role in SCLC progression and may be a promising target for therapy. Methods: Immunohistochemical staining was used to investigate the expression level of Fli-1 in 25 patients with SCLC, including 12 patients in limited stage and 13 patients in extensive stage. The growth, apoptosis assay and molecular mechanism of Fli-1 in SCLC cell line (NCI-H446) was studied by down-regulating Fli-1 expression through RNA interference. Results: It was shown that expression level of Fli-1 was significantly up-regulated in SCLC tissues compared with adjacent tissues (p=0.0002). Its staining was found specifically in the nuclei of cancer cells. Expression level of Fli-1 was higher in extensive stage disease than that in limited stage disease (p=0.0045). Down-regulation of Fli-1 expression by RNA interference in NCI-H446 was found to strongly decrease cell growth, promote cell apoptosis and reduce metastasis. Importantly, when Fli-1 was down-regulated in NCI-H446, epidermal growth factor (EGF)-induced Akt activation was dramatically decreased. It was implied that Fli-1 was involved in the Akt regulation passway. It was also confirmed that the apoptosis induced by decrease of Fli-1 expression via down-regulation of its target regulation gene, bcl-2. Conclusions: The novel mechanistic insight into a critical role of Fli-1 in SCLC progression was shown in this study. Fli-1 overexpression promotes SCLC aggression partly via activating Akt phosphorylation. We propose that Fli-1 is a new powerful predictor for SCLC progression, and is also a new potential target for SCLC treatment.