%0 Journal Article
%T Expression of human papilloma virus type 16 E5 protein in amelanotic melanoma cells regulates endo-cellular pH and restores tyrosinase activity
%A Fabio Di Domenico
%A Cesira Foppoli
%A Carla Blarzino
%A Marzia Perluigi
%A Francesca Paolini
%A Salvatrice Morici
%A Raffaella Coccia
%A Chiara Cini
%A Federico De Marco
%J Journal of Experimental & Clinical Cancer Research
%D 2009
%I BioMed Central
%R 10.1186/1756-9966-28-4
%X The expression of the HPV16-E5 oncoproteins was induced in two Tyrosinase-positive amelanotic melanomas (the cell lines FRM and M14) by a retroviral expression construct. Modulation of the intracellular pH was measured with Acridine orange and fluorescence microscopy. Expression of tyrosinase and its activity was followed by RT-PCR, Western Blot and enzyme assay. The anchorage-independence growth and the metabolic activity of E5 expressing cells were also monitored.We provide evidence that in the E5 expressing cells interaction between E5 and V-ATPase determines an increase of endo-cellular pH. The cellular alkalinisation in turn leads to the post-translational activation of tyrosinase, melanin synthesis and phenotype modulation. These effects are associated with an increased activation of tyrosine analogue anti-blastic drugs.Once expressed within intact human cells the HPV16-E5 oncoprotein does actually interact with the vacuolar V-ATPase proton pump and this interaction induces a number of functional effects. In amelanotic melanomas these effects can modulate the cell phenotype and can induce a higher sensitivity to tyrosine related anti-blastic drugs.Human Papillomavirus type 16 (HPV-16) is a member of species 9 of the mucosotropic ¦Á Papillomavirus genus. Together with a further fifteen ¦Á Papillomavirus types, HPV16 is comprised within the so called High Risk anogenital HPV (HR-HPV), that are causally involved in the development of malignant tumors [1]. In particular, HPV 16 is the major etiological agent for cervical cancer[2] and it has also been implicated as a causative agent in a number of carcinomas originating from a variety of other anatomical sites. The oncogenic potentials of HR-HPV types depend on the activity of three transforming genes: E5, E6, and E7. The E6 and E7 proteins are unanimously recognized as the major responsible for virus carcinogenicity [3-5]. Conversely, E5 has been found to have only weak transforming properties and accessory functio
%U http://www.jeccr.com/content/28/1/4