Date Completed: 1/14/09
Faculty Name: Hui Xu
UAB Department: Dermatology
UAB School: Medicine
Campus Address: VH 566B
Campus Zip: 0019
Telephone: 975-2628
Email Address: xuhui@uab.edu
Office Fax: 934-5745
Research Program Area: Cancer Cell Biology
Project Title: Mechanisms for Slit2 mediated suppression of tumor growth and metastasis
Project Status: Already up-and-running
Proposed Start Date: April 13
Proposed End Date: August 28
Number of Weeks of Internship: 16
Number of Interns: 1
Other faculty, staff, or graduate students who may help supervise intern: Dr. Donggou He; Hui Li
Expected Number of Work Hours Per Week: Negotiable
Expected Work Schedule for Intern: Flexible, intern can largely set his or her own schedule
Number of hours that preceptor will personally supervise or work with intern: 10
Category of Research: Laboratory Research
Cancer Research: Skin
Project Description: Slits are a group of secreted glycoproteins that play a role in the regulation of cell migration. Previous studies suggested that Slit2 might be a tumor suppressor gene. However, it remained to be determined whether Slit2 suppressed tumor growth and metastasis in animal models. We showed that Slit2 expression was decreased or abolished in human esophageal squamous cell carcinomas compared to normal tissues by in situ hybridization. Stable transfection of human squamous cell carcinoma A431 and fibrosarcoma HT1080 cells with Slit2 gene suppressed tumor growth in athymic nude mice. The apoptpsis in Slit2 transfected tumors was increased whereas proliferating cells were decreased, suggesting a mechanism for Slit2 mediated tumor suppression. This was supported by further analysis indicating that anti-apoptotic molecules and Bcl-2 and Bcl-xl and cell cycle molecules Cdk6 and Cyclin D1 were down regulated in Slit2 transfected tumors. Furthermore, wound healing and matrigel invasion assays showed that the transfection with Slit2 inhibited tumor cell migration and invasion. Slit2 transfected tumors showed a high level of keratin 8/18 and a low level of N-cadherin expression compared to empty vector-transfected tumors. More importantly, Slit2 transfection suppressed the metastasis of HT1080 tumor cells in lungs following intravenous inoculation. Collectively, our study has demonstrated that Slit2 inhibits tumor growth and metastasis of fibrosarcoma and squamous cell carcinoma and that the effect on cell cycle and apoptosis signal pathways is an important mechanism for Slit2 mediated tumor suppression. (Neoplasia. 10:1411-1420, 2008).
Intern's Anticipated Duties:
Duty 1: Cell cultures and in vitro assays for tumor growth, invasiveness and migration
Duty 2: Western blots for immunochemical identification of proteins
Duty 3: Immunohistochemical staining of tumor tissue sections and cells
Preceptor will provide intern with access to the following: office or desk space; computer and printer; laboratory work bench; equipment needed to complete project; supplies needed to complete project
Likelihood of authoring publications: Very Likely
Background, education, experience, or expertise preferred: Animal Research; Cell Biology; Basic Knowledge of Lab Skills; Biochemistry; Molecular Biology; Basic Knowledge of Statistics and Data Management
This faculty member will be a CaRES Preceptor for the first time.
Intern 1: Sandrine Niyongere