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Lu, Z. et al.

ETS2 is involved in protein kinase C-activated expression of granulocyte-macrophage colony-stimulating factor in human non-small lung carcinoma cell line, A549.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine expressed in the non-small lung carcinoma cells (NSCLC). However, transcriptional regulation of GM-CSF is not well characterized in NSCLC. In this study we found that two cis-acting ETS family consensus sites are important for transcriptional regulation of GM-CSF in A549 human lung carcinoma cells. These two sites are located separately at around -40 and -100 bp from the transcription start site. Results of transient transfection assays with A549 cells indicated that ETS2 had a strong positive effect on GM-CSF promoter activity. Furthermore, this activity was enhanced by protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), in an ETS consensus-dependent manner, while PMA could also enhance the expression level of ETS2. The protein kinase C inhibitors decreased GM-CSF promoter activity induced by the protein kinase C activator PMA. We also found that antisense ETS2 mRNA decreased PMA-induced GM-CSF promoter activity, supporting the possibility that ETS2 is involved in protein kinase C- induced GM-CSF transcriptional function. Endogenous expression of GM-CSF mRNA was increased by ETS2 transfection and the increased expression was further enhanced by PMA. These data indicate that GM-CSF is up-regulated by ETS2, a target of protein kinase C.[1]

References

ETS2 is involved in protein kinase C-activated expression of granulocyte-macrophage colony-stimulating factor in human non-small lung carcinoma cell line, A549. Lu, Z., Kim, K.A., Suico, M.A., Uto, A., Seki, Y., Shuto, T., Isohama, Y., Miyata, T., Kai, H. Biochem. Biophys. Res. Commun. (2003) [Pubmed]

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