Characterization of the role of Ki-1/57 in the development of colon cancer using the knock out mice for the Ki-1/57 gene as a model

• Grant number: 17/22064-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2018
• End date: January 31, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Jörg Kobarg
• Grantee: Flávia Regina Moraes da Silva
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Colon cancer is the third most frequent in men and the second in women, with increasing rates of morbidity and mortality in the world. Some studies suggest the involvement of genetic variants in the predisposition to colon cancer, such as chromosome locus 9q22.2-31.2 that has a linkage with familial colon cancer, where the Ki-1/57 gene is in imbalance. Ki-1/57 is a nuclear and cytoplasmic regulatory protein of 57 kDa, it was identified by its cross-reactant with the monoclonal antibodyKi-1, able to detect malignant cells in Hodgkin's lymphoma. The Dr. Jörg Kobarg team has been very active in study about proteins related to cancer, mainly the Ki-1/57.This protein is expressed in several types of cancer, and yeast two-hybrid system performed by the team showed its interaction with proteins involved in different pathways of DNA damage repair, suggesting a potential effect of this protein in the maintenance of DNA integrity. Additionally, the team has shown that knockout mice for the Ki-1/57 gene developed a greater number and size of colon tumors than wild animals, after Azoxymethane/Dextran Sulfate Sodium (AOM/DSS)-induced colon cancer associated to colitis, suggesting its role as a tumor suppressor for cancer colon. These results should be complemented by the present project, whose central objective is characterize the signaling pathways and cellular alterations involved in the susceptibility to the colon tumors development observed in knockout animals for the Ki-1/57 gene. Then, we will perform the following procedures: Chemically-induced colon tumors in knockout mice for Ki-1/57 (Group 1) and in wild mice (Group 2), transfer of tumor cells for in vitro assays, inoculation of this cells in knouckout mice (Group 3) and wild mice (Group 4). In another moment, we will perform complementation of Ki-1/57 in knouckout tumor cells and its inoculation in knouckout mice (Group 5), as well as, the Ki-1/57 gene deletion in wild tumor cells and its inoculation in wild mice (Group 6), aiming at a better understanding of the role of this protein in the colon cancer development.