C-Kit And RegⅣ Protein May Be Involved In The Pathogenesis Of Colorectal Cancer

Colorectal cancer is the third most common cancer in the world and the forth cause of cancer death. The incidence is approximately 1 000 000 cases per year and over 500,000 deaths per year. Approximately 25% of patients present with metastatic disease; the remaining 75% are treated surgically with cure as the objective, but even with complete resection the disease will eventually recur in 50% of these. Adjuvant therapy affords a risk reduction of at least one-third in stages II and III disease.The pathogenesis of colorectal cancer is of particular interest for the complex and only partially understood interaction between environmental factors and genetic background. The current model for colorectal carcinogenesis postulates a multistage progression involving an accumulation of gene mutations (APC, DCC,K-ras, p53, DNA mismatch repair genes), alterations in gene expression (c-myc, TGFL receptor), and chromosome losses, during which regulation of cell growth is disrupted. Advances in our understanding of the molecular mechanisms underlying the development and progression of cancer have resulted in the discovery of new therapeutic interventions that target specific molecular abnormalities. These molecular markers associated with either tumor biology, tumor burden, or host response are entering a critical phase in their evaluation.C-Kit is a type III receptor tyrosine kinase operating in cell signal transduction in several cell types. Normally C-Kit is activated by binding of its ligand, the stem cell factor. Such activation regulates apoptosis, cell differentiation, proliferation, chemotaxis, and cell adhesion. SCF and c-Kit have also been linked to several hematologic and non-hematologic neoplastic disorders. For example, gastrointestinal-stromal tumors (GIST) have activating mutations of Kit, thereby serving as an attractive therapeutic target. In breast tumor cells, small cell lung cancer cells, gynecological tumors and malignant glioma cells it has been suggested that autocrine production of SCF or Coexpression of SCF leads to a clonal expansion of c-Kit expressing cells. Recent studies have suggested that the presence of the SCF/c-Kit pathway may be an important regulator of proliferation and progression of human colorectal cancer, capable of affecting the prognosis of these patients. If present, the...