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Analysis of Microtubule Mediated Functions of Prostate Specific Membrane Antigen

Principal Investigator: RAJASEKARAN, AYYAPPAN
Program: PCRP
Proposal Number: PC010461
Award Number: DAMD17-02-1-0661
Funding Mechanism: Idea Development Award
Partnering Awards:
Award Amount: $572,197.00


Prostate specific membrane antigen (PSMA) is a plasma membrane protein expressed on the cell surface in prostate epithelial cells. This protein is expressed in large amounts in prostate cancer and metastatic deposits. The significance of increased expression of PSMA in prostate cancer is not known. Since PSMA is a plasma membrane protein, it is an ideal target for the immunotherapy for prostate cancer. We have shown that PSMA may have the function of a receptor internalizing a putative ligand. To better understand the internalization mechanisms of PSMA, we expressed PSMA in a normal epithelial cell line. We found distinct differences in the internalization mechanism of PSMA in prostate cancer and in a normal cell line. In prostate cancer cells, drugs that depolymerize microtubules did not affect PSMA internalization. In contrast, microtubule depolymerization dramatically reduced the internalization of PSMA in normal epithelial cells indicating that prostate cancer cells have altered the microtubule requirement for the internalization of PSMA. Microtubules are cytoskeletal elements that function as tracts for the movement of internalized vesicles to reach endosomes and lysosomes. The goal of this proposal is to unravel the role of microtubules in the internalization of PSMA in prostate and normal cell lines. Understanding the role of microtubules in PSMA internalization should provide more insights into the function of this molecule.