Study the Klf10 Alters Metabolic Pathways in Genetic-Deficient Mice and Human Pancreatic Ductal Carcinomas

Project: A - Government Institutionb - Ministry of Science and Technology

Description

Our previous studies have found that tumor suppressor gene KLF10 can regulate and inhibit the BI-1 gene expression, and leading to decrease the intracellular calcium level. The literatures have pointed out that BI-1 as a critical regulator of ER stress responses in the development of obesity-associated insulin resistance. Base on this correlation, we made a speculative hypothesis that the KLF10 knockout mice may present diabetic phenomena. In our current project, the KLF10 conventional knockout mice showed serial defects including glucose intolerance, hyperinsulinism, insulin resistance, significant HOMA-IR and pancreatic inflammation etc. Now, epidemiologic evidences suggest that people with diabetes are at a significantly higher risk of many forms of cancer including digestive-tract, liver and pancreatic cancers. But, mechanisms by which these factors or specific genes interact with cancer risk require further study. In this project, the pancreas and liver of KLF10-deficient mice will dissect and analyze by microarray and further pathway classification in first aim. Although still initiative, we have obtained probably candidates that up-expressed and involved in glucose and lipid metabolisms after conventional KLF10 knockout. With these information on hand, we will adopt KLF10-regulated metabolic pathway to verify correlation in culture cell, animal and clinical specimens. Moreover, this aims also will try to identify KLF10 related secondary metabolites that alters the expressional level in blood as a non-invasive maker next. In addition, tumor metabolism now is an important issue that targeting key metabolic enzymes or genes in tumors may open a new chapter in cancer treatment, which is well worth exploring. Finally, this integrated PPG-“The Role of KLF10 in Pancreatic Cancer Tumorigenesis and Its Application in Clinical Diagnosis” will be an initiative for identifying drug targets and developing effective therapeutics.
StatusFinished
Effective start/end date8/1/127/31/13