PMA Enhanced ESE-3 mRNA Expression in HO-1-N-1 Cell

Ets factors constitute one important class of transcriptional regulators that play critical roles in hematopoiesis, angiogenesis, organogenesis, oncogenesis, and specification of neuronal connectivity. Epithelium-specific Ets factor, family member-3 (ESE-3), a novel member of the ESE subfamily of Ets transcription factors is exclusively expressed in a subset of epithelial cells with highest expression in glandular epithelium. In order to clarify the mechanism of oral carcinogenesis, it is quite important to know the nature of ESE-3 in oral tissue. Objectives: The present study was investigated ESE-3 mRNA expression and regulation in buccal mucosa carcinoma-derived cell line, HO-1-N-1, epithelial-like cell. Furthermore, the effect of phorbol 12-myristate 13-acetate (PMA), protein kinase C (PKC) activator, was focused on ESE-3 mRNA expression. Methods: HO-1-N-1 cellls were treated with epidermal growth factor (EGF), transforming growth factor-β (TGF-β), PMA, PKC inhibitor (bisindolylmaleimide, BIS), MEK1/2 inhibitor (U0126) and/or P38 MAPK inhibitor (SB203580). RNA was isolated from HO-1-N-1 cells and ESE-3 mRNA expression was analyzed by RT-PCR. Results: PMA (0.1μM) increased ESE-3 mRNA expression at 6 hours, however, EGF (1μg/ml) and TGF-β (5ng/ml) did not alter it. ESE-3 mRNA expression elicited by PMA was inhibited by BIS (10μM) and U0126 (10μM). Conclusion: These results suggest that ESE-3 mRNA expression enhanced by PKC activator is regulated through MEK1/2 pathway in HO-1-N-1 cell. This study was supported in part by Grant-in-aids for 2003-Multidisciplinary Research Projects from MEXT and Scientific Research C-16591895 from JSPS.