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

Abstract

BackgroundEsophageal 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.MethodsSeventy 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.ResultsA 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.ConclusionDifferential 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.

Association of cyclin D1 gene polymorphisms with risk of esophageal squamous cell carcinoma in Kashmir Valley—A high risk area

“…Another factor that significantly contributed to elevated risk in cases was consumption of >3 cups of hot salted tea per day. This is in agreement with other studies from same region in esophageal cancer that showed a strong involvement of hot salted tea along with other genetic factors as a risk towards development of esophageal cancer [38]. The local residents of Kashmir valley prepare tea by using baking soda (sodium bicarbonate) and common salt and boil this tea for 2–3 h unless a thick red brown colored extract is obtained before its consumption.…”

“…The local residents of Kashmir valley prepare tea by using baking soda (sodium bicarbonate) and common salt and boil this tea for 2–3 h unless a thick red brown colored extract is obtained before its consumption. It has been assumed that the salts might cause thermal injury to esophageal lining [6] and also it has been reported that salted tea is rich in carcinogenic N ‐nitroso compounds containing approximately 3 ppm N ‐methylnitrosourea which promotes high methylating activity [5] and could possibly alter the activity and expression of host‐cell transcription factors [38].…”

“…It is imperative to add here that the current study was carried out in Kashmir valley, a high altitude area where people are homogamous and are exposed to extreme sunlight and have unique ethnic background, life style and food habit such as, eating of sun dried and pickled vegetables and highly spicy or oily food with a lot of red chillies and drink sodium bicarbonate brewed hot salted tea. Smoking cigarettes and other forms of tobacco preparations is also common among Kashmiri population [37, 38] and incidence of esophageal cancer is very high compared to other cancers.…”

Aberrant promoter methylation and loss of Suppressor of Cytokine Signalling-1 gene expression in the development of uterine cervical carcinogenesis

“…The blots were stripped and reprobed for β-actin levels to confirm equal loading and normalization. The expression levels of SOCS-1 were evaluated densitometrically by using digital image analysis (Image J software version 1.38, NIH USA) on a scale of 0-255 and the averaged pixel values were re-grouped for analysis on an arbitrary scale as strong =>50%; medium = 10-50%; weak = 1-10% and nil/not detectable <1% as described earlier [32] . Loss of SOCS-1 gene expression in tumor tissue was determined by quantitating and comparing it with SOCS-1 expression in normal tissues.…”

The Role of Glycogen Synthase Kinase 3-β in Immunity and Cell Cycle: Implications in Esophageal Cancer

“…Thus, summarizing the function of these TFs in the development of EC and the regulatory influence of GSK3b would direct us toward understanding the potential of GSK3b as a molecular target of EC and other cancers. AP-1, a dimeric transcription factor that is comprised of c-Jun and c-Fos, was shown to highly express in EC and was closely associated with the development of EC (Hussain et al 2009;Jimeno et al 2006). c-Jun has been reported to play a critical role in carcinogenesis and cell apoptosis via emigrating from the cytoplasm to the nucleus (Taira et al 2012;Wang et al 2011d).…”