Cyclooxygenase-2 Expression And Carcinogenesis Of Colorectum

Colorectal cancer is a common kind of gastrointestinal malignancy in both West and China, and is the second or third most common form of cancer worldwide. In Western countries, it is the second death cause by maliganant tumors. In China, the incidence of colorectal cancer and the death rate have been rising in recent years, it is the fourth to sixth form of death by maliganant tumors. With the changes of life cycle and diet, the risk of colorectal cancer will be increasing continuously. Therefore, it is very important to extensively identify the mechanism of colorectal carcinogenesis and find the ways to prevent the disease.The function and expression changes of cyclooxygenase family have been studied in different tumors. COX-2 is specially overexpressed in colorectal cancer. The mechanism of COX-2 overexpression is unclear, which may be associated with gene mutation, methylation and abnormal activation of signal transduction. Cyclooxygenases are key enzymes that convert arachidonic acid to prostaglandins, and the family has two isozymes: COX-1 and COX-2. COX-1 is a housekeeping gene and its expression is constitutive in almost all human tissues, but COX-2 expression is specific in a limited number of tissues. It has been suggested that expression of COX-2 in human tissue might be induced by growth factors, cytokine factors and some other factors. In gastrointestinal tissues, COX-1 can protect normal mucosa. COX-2 does not express in most tissues or expresses subtly but expresses highly in inflammatory tissues and tumor tissues. Actually it is a common opinion that the expression of COX-2 is concerned with many kinds of pathological processes. Many results reveal that COX-2 is related to the initiation and promotion of many kinds of tumors, specially in colorectal cancers. So it is necessary and important to investigatethe mechanism of COX-2 in carcinogenesis. The role of COX-2 expression in various stages of colorectal tumors remains to be elucidated.Wild-type p53 gene is the most important tumor suppressor gene in human. P53 gene mutation exsits in many kinds of human tumors. Its protein can combine with specific DNA sequence resulting in inhibiting or promoting the transcription of downstreaming genes. Gene mutation can inactivate associated functions. In normal cells, the half life of wild-type p53 is too short to be detected by imrnunohistochemistry. Mutation of p53 is thought to enlong the protein half-life and oncoprotein can be detected by immunohistochemistry in many kinds of tumors.In about half of colorectal cancers, the p53 gene mutation can be identified. In vitro data suggest that wild-type p53 could inhibit the transcription of COX-2 while in many kinds of tumors. COX-2 is overexpressed by p53 mutation. P53 inhibits COX-2 expression by blocking the binding of transcription protein to TATA box in promoter region of COX-2. P53 and COXs may play a critical role in colorectal carcinogenesis.The expression changes of COX-2 appeared in early stage of colorectal carcinogenesis. COX-2 can promote tumor cell growth, inhibit the tumor cell apoptosis and interact with many oncogenes and tumor suppressor genes. To investigate the clear mechanism of overexpression of COX-2 in colorectal cancer, we focused on the different expression of COX-2 between tumor tissues and normal mucosa tissues. COX-2 expression in different histological types and differentation of colorectal cancer was shown by immunohistochemistry and RT-PCR methods. The association of COX-2 expression with clinicopathological parameters and p53 expression was also intended yo be clear.One hundred and thirty-three patients with sporadic primary colorectal tumors undergoing curative resection between 1993 and 2000 were studied. All the specimens were obtained from department of pathology, first affiliated hospital. Detailed clinical pathological data were recorded. In total 40 adenomas and 93 adenocarcinomas wereused for COX-2 expression while among them 30 adenomas and 61 adenocarcinomas for p53. All the tissue specimens were preserved with 10% v/v for...