Abstract 2722: Transcription factor NF-kB in esophageal squamous cell carcinoma: Alterations in activity and expression during Human Papillomavirus infection

Abstract

Abstract Background: Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths in Jammu and Kashmir (J&K) region of India. A substantial proportion of esophageal carcinoma is associated with infection of high risk HPV type 16 and HPV18, the oncogenic expression of which is controlled by host cell transcription factor Nuclear factor kappa B (NF-kB). We therefore have investigated the role of DNA binding and expression pattern of NF-kB in esophageal cancer with or without HPV infection. Methods: Seventy five histopathologically-confirmed esophageal cancer and an equal number of corresponding adjacent normal tissue biopsies from Kashmir were analyzed for HPV infection, DNA binding activity and expression of NF-kB family of proteins by PCR, gel shift assay and immunoblotting respectively. Results: A high DNA binding activity and elevated expression of NF-kB proteins was observed in esophageal cancer tissue biopsies whereas, it was undetectable or reduced in all corresponding normal adjacent tissues but did not differ with respect to different grades of ESCC. In order to examine the composition of functional NF-kB complex both in HPV positive and negative esophageal tumors gel supershift assays were performed by adding specific antibodies to all 5 members of NF-kB family proteins (p50, p52, p65, RelB, and cRel). Supershift analysis revealed that p50 was a major binding partner and showed a preferential homodimerization in HPV negative esophageal tumors (61/75) and this participation was more evident in advanced grade of the disease (MDSCC+PDSCC; 46/61). On the other hand, HPV16 infected tumor tissues (n=14) showed hetrodimerization between p50 and cRel in more than 85% (12/14) of esophageal tumors. Interestingly, 2 cases with HPV infection p65 was also found to participate along with p50 and cRel in well-differentiated state of esophageal cancer. It is quite likely that the functional NF-kB complex formation in advanced grade of esophageal cancer comprises of p50/p50 homodimerization whereas in HPV infected esophageal tumors p50/cRel hetrodimerization occurs along with p65 in well differentiated state of the disease. Conclusion: Differential NF-kB dimerization and expression of its specific proteins between HPV – positive and HPV – negative cases indicate that NF-kB may play an important role during HPV induced esophageal carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2722. doi:10.1158/1538-7445.AM2011-2722