Our previous studies on cutaneous beta human papillomavirus 38 (HPV38) E6 and E7 oncoproteins highlighted a novel activity of IκB kinase beta (IKKβ) in the nucleus of human keratinocytes, where it phosphorylates and stabilizes ΔNp73α, an antagonist of p53/p73 functions. Here, we further characterize the role of the IKKβ nuclear form. We show that IKKβ nuclear translocation and ΔNp73α accumulati...

The proliferating cell nuclear antigen (PCNA) is essential for DNA replication of mammalian cells and their small DNA tumor viruses. The mechanism of the cell cycle-dependent regulation of the human PCNA promoter is not clear despite extensive investigations. In this report, we employed organotypic cultures of primary human keratinocytes, which closely resemble native skin comprising both proli...

Purpose: Imiquimod is a toll-like receptor 7 agonist used topically to treat external genital warts and basal cell carcinoma. We examined the combination of topical imiquimod with intramuscular administration of CRT/E7, a therapeutic HPV vaccine comprised of a naked DNA vector expressing calreticulin fused to HPV16 E7. Experimental Design: Using an orthotopic HPV16 E6/E7+ syngeneic tumor, TC-1,...

We have previously shown a functional interaction between human papillomavirus type 16 (HPV-16) E6 and E7 oncoproteins and cigarette smoke condensate (CSC) in lung cells suggesting cooperation during carcinogenesis. The molecular mechanisms of such interaction, however, remain to be elucidated. Here we first present evidence showing that cigarette smoke condensate (CSC) has the ability to activ...

To investigate E7-dependent biochemical changes which are involved in cellular transformation, we analyzed the influence of human papillomavirus type 16 (HPV-16) E7 on the expression of cell cycle regulatory proteins. Expression of E7 in established rodent fibroblasts (NIH 3T3), which was shown to be sufficient for transformation of these cells, leads to constitutive expression of the cyclin E ...

Cells arrest in the G1 or G0 phase of the cell cycle in response to a variety of negative growth signals that induce arrest by different molecular pathways. The ability of human papillomavirus (HPV) oncogenes to bypass these signals and allow cells to progress into the S phase probably contributes to the neoplastic potential of the virus. The E7 protein of HPV-16 was able to disrupt the respons...

High risk HPV infection is considered to play a central role in cervical carcinogenesis. HPV DNA testing has shown to be a very useful tool for screening and following cervical infections. The aim of this study was to compare three methods for HPV DNA detection, along with cytology and colposcopy analysis. Cervical samples were collected from 100 sexually active women in Mérida, western Venezue...

BACKGROUND Cervical cancer is the most prevalent tumor in developing countries and the second most frequent cancer among female population worldwide. Specific human papillomaviruses and, most notably, HPV types 16 and 18 are recognized as being causally associated with cervical carcinomas. The early HPV type 16 genes, E6 and E7, directly participate in the in vitro transformation of primary hum...

BACKGROUND Human papillomavirus (HPV) is a risk factor for head and neck cancers (HNC), yet HPV-associated tumors have better prognosis than HPV-negative tumors. METHODS We evaluated whether pretreatment presence of antibodies to HPV capsids [virus-like particles (VLP)] or to HPV-16 oncoproteins E6 and E7 was a predictor of HPV-positive HNC and clinical outcomes. Sera from 156 HNC patients we...

Aims Detection of E6 and E7 mRNA transcripts has been shown to be of higher prognostic value for the evaluation of the precursor lesions of cervical carcinoma than the detection of HPV DNA in a number of pilot studies [1-3]. In particular in low grade lesions, HPV DNA testing has poor discriminating power as to the progression of CIN, thus leading to considerable overtreatment with ensuing cost...