Sp1 Upregulates Survivin Expression in Adenocarcinoma of Lung Cell Line A549

Survivin has been implicated in tumor genesis, progression, and resistance to anticancer agents. However, the precise regulatory mechanism for survivin expression is not thoroughly defined. In this study, we showed that Sp1 was co-overexpressed with survivin in adenocarcinoma of lung cells A549, but not in differentiated human bronchial epithelial cells 4F0439 or small airway epithelial cells 3F1584. Subsequently, transfection experiments demonstrated that the inhibition of Sp1 signaling suppressed survivin expression in A549 cells, whereas Sp1 overexpression increased the level of survivin protein as well as its mRNA. We also found that Sp1 could decrease capase-9 activity, which is shown to be suppressed by survivin during apoptosis inhibition. Finally, Luciferase activity and ChIP assays revealed that Sp1 activated survivin promoter by direct interaction with it. Taken together, our data suggest Sp1 plays a potent role in the upregulation of survivin expression in lung cancer cells at the transcriptional level. Anat Rec, 294: 774-780, 2011. (C) 2011 Wiley-Liss, Inc.