Study on expression and mutation of epidermal growth factor receptor in the cell lines of oral squamous cell carcinoma in oral and maxillofacial region

Kim, Chul Hwan; Kim, Kyung Wook

Abstract

Carcinogenesis has been considered as multiple stage process of denaturation of gene which control regulation of cell growth. The growth and differentiation of oral mucosal cell is controlled by growth factors which regulate development and differentiation of cell and apoptosis. It is well known that the cell growth is not prevented, and secretion or reaction of growth factors is disturbed in head and neck carcinoma including oral carcinoma. The epidermal growth factor is a polypeptide with potent mitogenic activity of 6,045 daltons which has been shown to involve nuclear differentiation by trigger a cascade of intracellular ionic change and morphological transformation that it bind with epidermal growth factor receptor in surface of cells and delivering signal to inside of cells. The epidermal growth factor receptor is 170-kDa transmembrane phosphoglycoprotein. The extracelloular domain is binding site of epidermal growth factor, and intracellular domain possesses intrinsic tyrosine kinase activity, which the stimulation can lead to autophosphylation of epidermal growth factor receptor and sequences lead to phosphylation of target protein in case of epidermal growth factor bind with target cell surface receptor. In recently, expression of epidermal growth factor receptor has been detected in oral squamous cell carcinoma, and overexpression of it is proved, and possibility of early markers of carcinogenesis in head and neck is presented. The many studies for the expression of epidermal growth factor receptor and relationship between it and prognosis of malignancy in carcinoma of breast or stomach have documented. But, in oral squamous cell carcinoma, the study for difference of amplication and mutation of epidermal growth factor receptor gene between primary carcinoma and metastastic carcinoma is rare. For study on mRNA expression of epidermal growth factor receptor, normal human oral keratinocyte, and cell lines of primary and metastastic oral squamous cell carcinomas were cultured, and then, electrophoresis and T-PCR(Reverse Transcription-Polymerase Chain Reaction) were performed. The results were obtained as follows: The mutation of mRNA of EGF receptor were not detected in all oral squamous carcinoma cell lines. The expression of EGF receptor in oral squamous cell lines expressed 3-7 times higher than that of normal human oral keratinocyte in cytoplasmic domain, and 2-3 times higher in extracellular domain. The expression of EGF receptor of cytoplasmic domain more expressed than that of extracellular domain in primary squamous cell line. The expression of EGF receptor in metastastic carcinoma cell lines is similiar or underexpressed than that of normal human oral keratinocyte cell lines. The expression of EGF receptor in the primary carcinoma cell lines expressed 2-5 times higher than that of metastastic carcinoma cell lines. From the results obtained in this study, the mutation have not detected in mRNA of EGF receptor in carcinoma cell lines, and EGF receptor was ooverexpressed in early stage of carcinogemesis, and cytoplasmic domain of EGF receptor have relation with carcinogenesis and EGF receptor have no relation with metastasis.