List of Abbreviations used bFGF basic fibroblast growth factor. BrdU bromodeox yuridine. Col I collagen I. DMEM Dulbeccos modified Eagles medium. DMSO dimethyl sulfoxide. EGF epi dermal growth cell assay factor. EGFR epidermal growth factor receptor. FCS fetal calf serum. Fn fibronectin. HB EGF heparin binding epidermal growth factor. HERmrk human EGF receptor Inhibitors,Modulators,Libraries Xmrk chimeric protein. IGFBP insulin like growth factor binding protein. MAPK mitogen activated protein kinase. MEK mito gen activated protein kinase kinase. MMP matrix metal loprotease. PBS phosphate buffered saline. PDGF platelet derived growth factor. PI3K phosphoinositide 3 kinase. RTK receptor tyrosine kinase tetradecanoyl phorbol 13 acetate. Tyr tyrosinase. Vn vitronectin. WCL whole cell lysate. Xmrk Xiphophorus melanoma receptor kinase.

Background p53, a major tumor suppressor or guardian of the gen ome is mutated, deleted or inactivated in various can cers. Almost all human papillomavirus Inhibitors,Modulators,Libraries infected cancer cells contain wild type p53. p53 is non functional Inhibitors,Modulators,Libraries as HPVE6 protein abrogates its function either by ubiquitin dependent and independent degrada tion, by inhibition of acetylation or by repressing p53 dependent downstream molecular pathways. Though, E6 associates with p53 for its degradation . there are contradictory reports on the inhibition and activation of p53 pathways by E6. Ectopic expression of p53 in cancer cells lacking p53 or harboring mutant and/or abrogated wild type p53, have contrasting effects on cell fate. In p53 null cancer cells, p53 overexpression causes cell cycle arrest and apoptosis.

However, in virus infected cells harboring wild type p53, overexpression of p53 does not induce cell Inhibitors,Modulators,Libraries cycle arrest and apoptosis. Till date there are only three reports describing the consequences of p53 overexpression in HPV positive cells and results obtained leave ample scope for debate. Disparity among these reports may be due to Inhibitors,Modulators,Libraries differences in ade noviral multiplicity of infection. Taken together, the role of p53 overexpression in HPV positive cells remains obscure. In HPV positive cells, E6 works at different hierarchal levels in p53 pathway. It degrades p53, p21 and Bax causing impairment in cell cycle arrest/apopto sis and making p53 activation more difficult. With recent developments in efficient gene delivery systems and the prospect of gene therapy making a come back its likely that p53 based therapy may become a reality.

useful site p53 executes its tumor suppressor activity by triggering cell cycle arrest and apoptosis. However, the factors that facilitate selection between cell cycle arrest and/or apoptosis are not well under stood. It has been reported that p21 is most important transcriptional targets of p53 for causing cell cycle arrest and p53 executes apoptosis through Bax transcrip tion. To study the role of p53 in E6 positive cells, we developed a novel isogenic HeLa cells with Tet On regulated p53 expression.