ABSTRACT
During laryngeal carcinogenesis, a variety of genomic imbalances are involved in hyperplastic and dysplastic laryngeal epithelia as early or progressive genetic events, respectively. Oncogenes' overactivation is a crucial genetic event in malignant and pre-malignant neoplastic epithelia. Especially, deregulation of crucial pathways including transcription factors - such as c-Fos and c-Jun - leads to an aberrant expression of other crucial genes responsible for cell homeostasis. Upregulation of c-Fos and c-Jun proto-oncogenes -due to increased copy numbers (amplification) or intra-genic point mutations- seems to be correlated with aggressive biological behaviour in laryngeal squamous cell carcinomas (LSCCs). In the current special molecular article we explored the role of c-Fos/c-Jun complex deregulation in LSCC.
Subject(s)
Laryngeal Neoplasms/genetics , Proto-Oncogene Proteins c-fos/genetics , Proto-Oncogene Proteins c-jun/genetics , Squamous Cell Carcinoma of Head and Neck/genetics , Animals , Genes, fos , Genes, jun , Humans , Laryngeal Neoplasms/metabolism , Proto-Oncogene Proteins c-fos/metabolism , Proto-Oncogene Proteins c-jun/metabolism , Signal Transduction , Squamous Cell Carcinoma of Head and Neck/metabolismABSTRACT
Head and neck squamous cell carcinoma (HNSCC) includes a variety of SCCs derived from the anatomic regions of the oral and nasal cavity and also of the pharynx and larynx. Oral cavity SCC (OCSCC) demonstrates an increasing rate due to viral -related (High Risk Human Papilloma Virus-HR HPV) persistent infection, cigarette smoking and alcohol consumption. Gross chromosomal alterations (polysomy, aneuploidy) and specific gene aberrations such as amplifications, deletions, point mutations combined or not with epigenetic ones (promoter methylations and miRNA deregulations) are responsible for the progressive transformation of normal squamous epithelia to the corresponding malignant. In the majority of OCSCC cases, critical genes, such as p53 are found to be inactivated, leading to an overactivated cell cycle correlated to carcinogenetic process. P53 (gene location: 17p13.1) is a suppressor gene acting as a key regulator of the cell's genomic stability, function and homeostasis. P53 aberrant overexpression is frequently observed in OCSCC tissues as a result of point mutation or deletion. In the current special article we explored the role of the p53 gene deregulation - especially focused on its mutation status - in OCSCCs.