Transcription factor AP-1 in esophageal squamous cell carcinoma: alterations in activity and expression during human Papillomavirus infection

• Published in: BMC cancer Vol. 9; no. 1; p. 329
• Main Authors: Hussain, Showket, Bharti, Alok C, Salam, Irfana, Bhat, Mohammad Akbar, Mir, Mohammad Muzaffar, Hedau, Suresh, Siddiqi, Mushtaq A, Basir, Seemi Farhat, Das, Bhudev C
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 16.09.2009; BioMed Central; BMC
• Subjects: Adult; Aged; Aged, 80 and over; Alphapapillomavirus - physiology; Binding sites; Biomedical research; Cancer therapies; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - virology; Cervical cancer; Complications and side effects; Deoxyribonucleic acid; DNA; Dysphagia; Esophageal cancer; Esophageal Neoplasms - genetics; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - virology; Female; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; Genetic testing; Human papillomavirus; Humans; India; Male; Middle Aged; Papillomavirus infections; Papillomavirus Infections - genetics; Papillomavirus Infections - metabolism; Papillomavirus Infections - virology; Physiological aspects; Protein Binding; Risk factors; Studies; Surgery; Thoracic surgery; Transcription Factor AP-1 - genetics; Transcription Factor AP-1 - metabolism; Transcription factors; Tumors; India
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/1471-2407-9-329

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 Activator Protein-1 (AP-1). We, therefore, have investigated the role of DNA binding and expression pattern of AP-1 in esophageal cancer with or without HPV infection. 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 AP-1 family of proteins by PCR, gel shift assay and immunoblotting respectively. A high DNA binding activity and elevated expression of AP-1 proteins were observed in esophageal cancer, which differed between HPV positive (19%) and HPV negative (81%) carcinomas. While JunB, c-Fos and Fra-1 were the major contributors to AP-1 binding activity in HPV negative cases, Fra-1 was completely absent in HPV16 positive cancers. Comparison of AP-1 family proteins demonstrated high expression of JunD and c-Fos in HPV positive tumors, but interestingly, Fra-1 expression was extremely low or nil in these tumor tissues. Differential AP-1 binding activity and expression of its specific proteins between HPV--positive and HPV--negative cases indicate that AP-1 may play an important role during HPV-induced esophageal carcinogenesis.