Modulation by EGF and TGF-b1 in HNSCC

PITX1 and TGIF1 are homeobox genes involved with many aspects of the development and embriogenesis. Both have been described deregulated in several cancers and involved with RAS and TGF-b signaling pathways. Unfortunately, their role in carcinogenesis, mainly head and neck squamous cell carcinomas (HNSCC), remains unclear and poorly characterized. Objectives: To investigate the influence of EGF and TGF-b1 in the expression profile of PITX1 and TGIF1 using a primary and metastatic HNSCC cell lines (HN-6 and HN-31, respectively), and one non-cancerous cell line (HaCaT). Methods: All cell lines were treated with EGF and TGF-b1. The same cells, cultured without any treatment served as controls. Specific primers were designed for the analyzed genes and qPCR was performed using HPRT gene as loading control. A relative quantification based on the ΔCt method was done and the data were analyzed statistically by ANOVA two factors and Tukey's test (post hoc). Results: In general, both EGF and TGF-b1 were able to induce statistically different PITX1 and TGIF1 expression in the three cell lines. Both genes were upregulated in primary and metastatic HNSCC cell line when treated with TGF-b1. The opposite result was observed when EGF was used as treatment, which downregulated PITX1 and TGIF1 expression in HN-6 and HN31. Conclusion: Data presented suggest that PITX1 and TGIF1 are candidates to oncogenes in HNSCC. Besides, it is suggested a hypothetical role for this two homeobox genes, particularly TGIF1, in antagonizing the TGF-b-dependent anti-proliferative response. A search for a regulator of PITX1 and TGIF1 levels in vivo is encouraged.