? ? Colorectal cancer is a leading cause of cancer-related death in western countries. In recent decades, increased understanding of tumor molecular biology has led to the discovery of biological marker of cancer which help the detection and diagnosis. A number of biomarkers have been discovered, however, the diversity of genetic alterations which cells accumulate during the development from adenoma to carcinoma, necessitate the identification of novel biomarkers. Small GTPase Rac1b is a protein which belongs to the Rho family of small GTPases. Rho GTPase proteins are well known for their regulation of cell proliferation, transformation, apoptosis and motility, and as key players in oncogenesis and metastasis of various cancers. Rac1b was shown to induce malignant transformation in mouse mammary epithelial cells, and promote cell survival and cell-cycle progression in mouse fibroblasts. The striking characteristic of the Rac1b expression profile is that it is significantly increased in colorectal tumors compared to normal mucosa, and it was detected in 100% of liver metastatic tumor samples. These findings place Rac1b as a potential biomarker for colorectal cancer. The early detection of Rac1b will contribute to the current approaches in preventing the disease advancement. In this proposal, we aim to a) investigate the role of Rac1b in the regulation of cell growth, transformation and invasion of colorectal cancer cells, in a cell culture system as well as a mouse model, and b) statistically assess the association of Rac1b expression with the disease stages of human colorectal cancer. Because of insufficient biomarkers for colorectal cancer, the findings from this study will provide a better indicator of the disease progression and as such will be a useful tool for determination the course of treatment. ? ? ?
