Comparative study between the Hybrid Capture II test and PCR based assay for the detection of human papillomavirus DNA in oral submucous fibrosis and oral squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Oral malignancy is a major global health problem. Besides the main risk factors of tobacco, smoking and alcohol, infection by human papillomavirus (HPV) and genetic alterations are likely to play an important role in these lesions. The purpose of this study was to compare the efficacy of HC-II assay and PCR for the detection of specific HPV type (HPV 16 E6) in OSMF and OSCC cases as well as find out the prevalence of the high risk HPV (HR-HPV) in these lesions.</p> <p>Methods and materials</p> <p>Four hundred and thirty patients of the potentially malignant and malignant oral lesions were taken from the Department of Otorhinolaryngology, Moti Lal Nehru Medical College, Allahabad, India from Sept 2007-March 2010. Of which 208 cases were oral submucous fibrosis (OSMF) and 222 cases were oral squamous cell carcinoma (OSCC). The HC-II assay and PCR were used for the detection of HR-HPV DNA.</p> <p>Result</p> <p>The overall prevalence of HR-HPV 16 E6 DNA positivity was nearly 26% by PCR and 27.4% by the HC-II assay in case of potentially malignant disorder of the oral lesions such as OSMF. However, in case of malignant oral lesions such as OSCC, 32.4% HPV 16 E6 positive by PCR and 31.4% by the HC-II assay. In case of OSMF, the two test gave concordant result for 42 positive samples and 154 negative samples, with an overall level of agreement of 85.4% (Cohen's kappa = 66.83%, 95% CI 0.553-0.783). The sensitivity and specificity of the test were 73.7% and 92.05% (p < 0.00). In case of OSCC, the two test gave concordant result for 61 positive samples and 152 negative samples, with an overall level of agreement of 88.3% (Cohen's kappa = 79.29, 95% CI 0.769-0.939) and the sensitivity and specificity of the test were 87.14% and 92.76% (p < 0.00).</p> <p>Conclusion</p> <p>This study concluded that slight difference was found between the positivity rate of HR-HPV infection detected by the HC-II and PCR assay in OSMF and OSCC cases and the HC II assay seemed to have better sensitivity in case of OSCC.</p

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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p

C-Fos expression is a molecular predictor of progression and survival in epithelial ovarian carcinoma

Members of the Fos protein family dimerise with Jun proteins to form the AP-1 transcription factor complex. They have a central function in proliferation and differentiation of normal tissue as well as in oncogenic transformation and tumour progression. We analysed the expression of c-Fos, FosB, Fra-1 and Fra-2 to investigate the function of Fos transcription factors in ovarian cancer. A total of 101 patients were included in the study. Expression of Fos proteins was determined by western blot analysis, quantified by densitometry and verified by immunohistochemistry. Reduced c-Fos expression was independently associated with unfavourable progression-free survival (20.6, 31.6 and 51.2 months for patients with low, moderate and high c-Fos expression; P=0.003) as well as overall survival (23.8, 46.0 and 55.5 months for low, moderate and high c-Fos levels; P=0.003). No correlations were observed for FosB, Fra-1 and Fra-2. We conclude that loss of c-Fos expression is associated with tumour progression in ovarian carcinoma and that c-Fos may be a prognostic factor. These results are in contrast to the classic concept of c-Fos as an oncogene, but are supported by the recently discovered tumour-suppressing and proapoptotic function of c-Fos in various cancer types

Emerging roles of ATF2 and the dynamic AP1 network in cancer

Cooperation among transcription factors is central for their ability to execute specific transcriptional programmes. The AP1 complex exemplifies a network of transcription factors that function in unison under normal circumstances and during the course of tumour development and progression. This Perspective summarizes our current understanding of the changes in members of the AP1 complex and the role of ATF2 as part of this complex in tumorigenesis.Fil: Lopez Bergami, Pablo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Lau, Eric . Burnham Institute for Medical Research; Estados UnidosFil: Ronai, Zeev . Burnham Institute for Medical Research; Estados Unido

GP96 Interacts with HHV-6 during Viral Entry and Directs It for Cellular Degradation

CD46 and CD134 mediate attachment of Human Herpesvirus 6A (HHV-6A) and HHV-6B to host cell, respectively. But many cell types interfere with viral infection through rapid degradation of viral DNA. Hence, not all cells expressing these receptors are permissive to HHV-6 DNA replication and production of infective virions suggesting the involvement of additional factors that influence HHV-6 propagation. Here, we used a proteomics approach to identify other host cell proteins necessary for HHV-6 binding and entry. We found host cell chaperone protein GP96 to interact with HHV-6A and HHV-6B and to interfere with virus propagation within the host cell. In human peripheral blood mononuclear cells (PBMCs), GP96 is transported to the cell surface upon infection with HHV-6 and interacts with HHV-6A and -6B through its C-terminal end. Suppression of GP96 expression decreased initial viral binding but increased viral DNA replication. Transient expression of human GP96 allowed HHV-6 entry into CHO-K1 cells even in the absence of CD46. Thus, our results suggest an important role for GP96 during HHV-6 infection, which possibly supports the cellular degradation of the virus