Regulation of Prostate-Specific Antigen Expression by the Junctional Adhesion Molecule A

Objective: Prostate-specific antigen (PSA) is a protein specifically expressed in prostate cells. Therefore, the expression levels of PSA in the blood are an important indicator when diagnosing prostate cancer. Defining the mechanism of PSA expression in prostate cells will be helpful for interpreting the expression of this protein during prostate cancer progression. Reports show that a membrane protein, claudin-7 (CLDN-7), is involved in the expression of PSA. However, the mechanism by which CLDN-7 regulates PSA expression is not clear. Here we identify proteins that interact with CLDN-7 and determine whether such proteins can regulate PSA expression in a pattern similar to that of CLDN-7. Methods: Our previous studies have demonstrated that in prostate cells, PSA can be regulated by a membrane protein, CLDN-7. It is important to identify the proteins that associate with CLDN-7 in its pathway of regulating PSA expression, because it is very unlikely that CLDN-7 can directly regulate PSA expression in the nucleus. To identify potential proteins that may directly interact with CLDN-7, we studied proteins that can interact with claudins. Results: We found that CLDN-7 interacts with the junctional adhesion molecule A (JAM-A), which is expressed in the prostate cancer cell line, LNCaP, which expresses PSA, but not the PSA-negative prostate cell line, DU145. JAM-A regulates the expression of the prostate-specific antigen in LNCaP cells in a pattern similar to CLDN-7. Conclusions: Our results suggest that JAM-A associates with CLDN-7 and it is a component in the pathway by which CLDN-7 regulates the expression of PSA.