Experimental Study of Malignant Progression and Cell Bioligic Features on Oral Sqamous Cell Carcinoma

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MAP kinase family consists of a group of serine/threonine kinases that are activated by extracellular signals and play an integral role in regulating many cellular processes by transducing signals via receptors on the plasma membranes to nuclei. In particular, ERK (extracellular signal regulated protein kinase) is considered to be positioned in the transduction pathway of cell proliferation signal to nuclei and contribute to cell transformation. Indeed, ERK is constitutively expressed in neoplastic cells. Here, we attempted to examine the possible activation of protein kinase, especially ERK belonging to a MAP kinase family in association with malignant progression of carcinoma in the oral cavity. In cultured SCCTF cell lines established from squamous cell carcinomas of the oral cavity showing decreased sensitivity to bleomycin (BLM), significantly high ERK levels were constitutively expressed. ERK levels in these cells were not affected by the duration of incubation in the presence of BLM.Regarding biopsy specimens from oral carcinomas, there was a positive correlation between the cell proliferation and elevated ERK levels. Although there was no correlation between the ERK levels and grades or cell differentiation, less differentiated carcinomas tended to show higher incidences of Ki-67 positive cells in the tumor and also higher incidences of double positive cellss for Ki-67 and ERK.Thus, in poorly differentiated oral carcinoma, there was a positive correlation between the levels or ERK expression and cell proliferation, and between the levels of ERK expression and more highly malignant tumor accompanied by increased resistance to antitumor drugs. There positive correlations may indicate that the increased ERK expression led to accelerated cell cycle progression including induction of DNA synthesis. We conclude that ERK may play an important role in the processes of proliferation and malignant progression in squamous cell carcinoma of the oral cavity.