Downregulation of stathmin expression is mediated directly by Egr1 and associated with p53 activity in lung cancer cell line A549

Stathmin is overexpressed in a variety of assessed human malignancies and is correlated with tumor progression and poor prognosis. Downregulation of its expression will contribute to optimize therapeutic outcomes in the treatment of various malignancies. However, the mechanisms of stathmin gene overexpression are not completely elucidated at present. Early growth response 1 (Egr1) is a transcription factor that triggers transcription of downstream genes mediating cell growth and angiogenesis upon various stimulations. Following the previous computational identification of a site that was thought to be an Egr1 consensus binding sequence at -85 to -94 region in stathmin gene promoter, we analyzed the role of Egr1 in the regulation of stathmin gene expression in lung cancer cell line A549. The results showed that Egr1 transcription factor bound to the sequence 5'-GCGGGGGCG-3' within human stathmin gene promoter; and in reporter gene assays and overexpression experiments, both stathmin gene promoter activity and stathmin gene expression level were downregulated following endogenous or exogenous expression of Egr1. Using wild type Egr1 and knockout Egr1 cell lines, we demonstrated that p53 negatively regulates stathmin expression through Egr1 pathway. In summary, Egr1 is a novel regulator of stathmin expression and p53 mediates the transcriptional repression of stathmin by Egr1 in human lung cancer cells.