Request for Funding

Medical Student Research Fellowship for Summer 2001

Mentor: Donald P. Lombardi, M.D.

Department: Internal Medicine

Hamon Center for Therapeutic Oncology Research

Room number: NB8.224

Mail Code: MC 8593

Phone number: 214.648.1263

E-mail: Donald.Lombardi@utsouthwestern

Project title: Construction and analysis of a stable transfection of the metastasis suppressor gene, Kai1/CD82, in a gene-amplified Her-2/neu breast cancer cell line

Human subjects IRB approved project number (where applicable): N/A

Animal subjects IRB approved project number (where applicable): N/A

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects) Basic Science

Brief Description of Project:

KAI1/CD82 is a metastasis suppressor gene whose gene product encodes for a cell-surface protein consisting of four transmembrane domains and a large extracellular domain that is extensively glycosylated. In our laboratory, we found that down-regulation of KAI1 expression was observed in the progression from adjacent, non-malignant colonic mucosa to primary colonic tumor to liver metastases in samples procured from the same patients. We measured KAI1 protein expression using the C33 KAI1 monoclonal antibody and optimizing the detection of KAI1 antigen in frozen sections by immunohistochemical techniques. We have identified a KAI1 negative, HER-2/neu gene amplified breast cancer cell line, HCC 1007, that will serve as a model to test the following hypothesis: that because HER-2/neu gene amplification is associated with poor prognosis in women with breast cancer, we surmise that there will be an inverse correlation between gene amplification of HER-2/neu and the loss of expression of KAI1. Our goal is to transfect wild-type KAI1 into HCC 1007, and ask whether the metastatic phenotype is diminished with respect to cellular adhesion, invasion, and motility, three core characteristics of the metastatic phenotype.

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