Transactivation and expression patterns of Jun and Fos/AP‐1 super‐family proteins in human oral cancer

Abstract Transcription factor activator protein‐1 (AP‐1) super‐family is known to modulate expression of array of genes during development of many cancers and considered as an important target for modern therapeutics. But the role of AP‐1 during development of human oral cancers is still poorly understood. Because oral cancer is one of the most common cancers in India and south‐east Asia, we studied the activation and expression pattern of AP‐1 family of proteins and mRNA in different stages of oral carcinogenesis. Gel‐shift assay, western blotting, immunohistochemistry and northern blotting have been used to assess the binding activity and expression pattern of AP‐1 family (c‐Jun, JunB, JunD, c‐Fos, FosB, Fra‐1 and Fra‐2) proteins and mRNA transcripts in a total of 100 fresh oral tissue specimens comprising precancer ( n = 40), cancer ( n = 50) and healthy control ( n = 10). Constitutive activation of AP‐1 with concomitant upregulated expression of majority of AP‐1 family of proteins and mRNA was observed in cancer cases. Interestingly, almost all precancerous cases showed JunD homodimers, whereas c‐Fos/JunD was the most prevalent complex found in cancer tissues. The overexpression of EGFR mRNA, p50:p50/NF‐κB homodimer formation, together with overexpression of pERK and c‐Fos proteins in this study suggests an interesting cross talk between AP‐1 and NF‐κB pathways in oral cancers. Thus, this study demonstrates differential expression and activation of AP‐1 super‐family proteins in relation to severity of lesion and their crucial role in human oral carcinogenesis.