Estimation of prognosis and biological behavior of head and neck cancer is primarily based on clinicopathological parameters, mainly on tumor site and regional lymph node involvement. However, it is well known that tumors of the same clinicopathological stage can behave differently, especially in regard to the risk of tumor recurrences. Therefore, current work is focusing on the evaluation of molecular parameters to differentiate and complete the prognostic statement, which is critical to refine and improve treatment strategies [
12]. The pituitary tumor-transforming gene is a recently characterized oncogene, originally isolated by its differential expression in pituitary tumor cells [
1]. PTTG mRNA and protein is overexpressed in a variety of carcinomas [
4,
6,
14,
15], suggesting that PTTG may be involved in tumorigenesis. In addition to its function as human securin during the cell cycle, recent studies convincingly demonstrate that PTTG acts as a transcriptional activator. This function seems to be regulated by the activation of the mitogen-activated protein kinase cascade (MAPK) by epidermal growth factor (EGF). The interaction of PTTG with activated MAP kinase kinase (MEK-1) is crucial for the transactivation function of PTTG [
18]. The MAPK-pathway is known to be important in the regulation of cell growth, apoptosis and differentiation. Numerous studies reported a correlation between over-expression of the epidermal growth factor receptor (EGFR, c-erbB1) and poor prognosis in head and neck squamous cell carcinomas [
19]. Moreover, it has been demonstrated that MAPK activation regulates rat PTTG translocation into the nucleus where it is able to transcriptionally activate the oncogene
c-myc in vitro. [
20]. This might be of special interest, because
c-myc is known to play a critical role in the control of cellular proliferation and deregulation of
c-myc is associated with a variety of tumors. In human cancer, overexpression of c-myc protein stimulates cell cycle progression, leads to transformation and blocks differentiation [
21]. The induction of
c-myc expression by overexpression of PTTG results in increased cell proliferation and colony formation, strengthening the idea of PTTG playing an important role in the regulation of cell growth [
18]. Furthermore, PTTG also induces basic fibroblast-growth factor (bFGF) secretion, indicating a role of PTTG in tumor angiogenesis [
13,
22,
23] that is essentially required for tumor survival. Altogether, these observations underline the role of PTTG in development and maintenance of neoplastic processes.