TP53 Gene Signaling Pathways and Protein Interactions with MDM2 and HPV in Oral Cancers andndash; A Review

Oral cancers are heterogeneous group of tumors in topography (they can be localized at on the lips, tongue, upper and lower gums, hard and soft palates, floor of mouth, retromolar region, or inside of cheek), histologic forms (that can be carcinoma, sarcoma, lymphoma, melanoma or cylindroma) and clinical outcomes (good or poor prognosis). However, more than 50% of these cancer phenotypes express a mutation at TP53 gene while in the other 50% of cases; the TP53 protein pathway is often partially inactivated. In cancerous tissues, particularly in oral squamous cells, the loss of function at TP53 gene is associated with three molecular causes: (1) The genotoxic effect of risk factors such as alcohol abuse, tobacco smoking or betel nut chewing, (2) The inhibitory effect of the TP53 antagonist genes such as MDM2, or (3) The action of oncoproteins of high-risk human papillomavirus (HPV). This paper attempts firstly to make an exhaustive review of TP53 gene signalling pathways in normal and stressed cells, and secondly to describe in oral cancers the genetic events that occur at different steps of carcinogenesis after a loss of function in TP53 encoded protein.