Investigation of Highly Invasive Genes and Establishment of Molecular Targeting Modulation Model in Oral Cancer Cells (I)

Oral cancer is the sixth most frequent cancer in the world with an estimated over 500,000 new cases being diagnosed annually. The overall 5-year survival rate for patients with oral cancer is among the lowest of the major cancers, and has not changed during the past two decades. In Taiwan, the incidence of oral cancer has become the 7th leading cancer, the 5th leading cancer in male, and is still increasing in the recent years. Since this cancer usually occurs in the middle age male, at the high peak of life responsibility, it has tremendous impact of family and society. For treatment, although local control and survival rates are acceptable for early staged tumor, in advanced tumor, bulk tumor or lymph node metastasis is the common cause of treatment failure. The molecular factors predicting tumor invasion and metastasis have not been extensively studied, far away from clinical application of molecular adjuvant therapy. The aim of this study is to identify the genetic alterations associated with cellular invasion in cells from oral cancers by using cDNA microarray and proteomic technologies. Following identify, we will establish the molecular targeting therapeutic model in cultured cell, by cloning and modulating the gene expressions, aiming to alteration of cellular invasive ability. In addition, expression levels of the highly invasive genes in oral cancer tissue samples will be determined and the correlation study with clinical outcome will be analyzed to establish the clinical association. The specific aims and tentative schedule for this proposed project is listed bellows. First year: Establishment of the highly invasive cell model and identification of the genes A. To establish highly invasive sbuclones of oral cancer cells. B. Global survey highly invasive genes using microarray and proteomic techniques. Second to third year: Cloning of the highly invasive gene and establishment of the molecular targeting therapeutic model in cultured cells A. Construction of the gene expression vectors (for down-regulatory gene) or RNA interference vectors (for up-regulatory genes), and transfection of the genes into highly invasive cells. B. Functional analysis of the altered gene in cell status, including cell growth/viability, colony formation, cell cycle distribution and invasion ability. Third year: Examination and clinical association study of the highly invasive genes on oral cancer patients A. Evaluating the expression levels of the invasive genes in oral cancer patient samples. B. Correlation of the gene expression with the cliniclpathological features and the treatment outcome.

Project ID:PC9308-2403
External Project ID:NSC93-2745-B182-005-URD