Relationship between protease activity and neu oncogene expression in patients with oral leukoplakia treated with the Bowman Birk Inhibitor

The protease catalyzing the hydrolysis of the tripeptide fluorescence subst rate, butoxycarbonyl-valine-proline-arginine-(7-amino-4-methylcoumarin) (Bo c-Val-Pro-Arg-MCA) and the neu oncogenic protein are potentially useful bio markers for human cancer prevention studies. In the present study, we stand ardized a specific substrate hydrolysis method for measuring this protease activity in human oral mucosal cells and characterized the relationship bet ween neu oncogene expression and protease activity in patients enrolled in an oral cancer prevention trial using Bowman Birk Inhibitor Concentrate (BB IC) as the cancer preventive agent. The results demonstrate that changes in the protease activity in oral mucosal cells after BBIC treatment correlate d with the changes in the neu protein levels in oral mucosal cells (r = 0.7 26, P < 0.001) and serum (r = 0.675, P < 0.001), suggesting that the Boc-Va l-Pro-Arg-MCA hydrolyzing activity can be as useful as neu oncogene express ion as a cancer biomarker, In the 25 patients enrolled in the study, the le vel of neu protein in oral mucosal cells correlated with the serum neu prot ein concentration in the patients before BBIC treatment (r 0.645, P < 0.001 ), However, such a correlation was not observed after the BBIC treatment, s uggesting that BEI may inhibit serine protease(s) involved in the cleavage of neu protein on the cell surface, thereby preventing the release of the e xtracellular domain of neu protein into the circulation. By inhibiting the cleavage of neu protein on the cell surface, BBI could prevent malignant an d premalignant cells expressing high levels of neu protein antigen from esc aping host immunological surveillance control.