1. Relationship between protease activity and neu oncogene expression in patients with oral leukoplakia treated with the Bowman Birk Inhibitor.
- Author
-
Wan, X S, Meyskens, F L, Jr, Armstrong, W B, Taylor, T H, and Kennedy, A R
- Subjects
Cell Transformation ,Neoplastic: drug effects ,genetics ,Cells ,Cultured ,Dose-Response Relationship ,Drug ,Gene Expression Regulation ,Neoplastic: drug effects ,Humans ,Leukoplakia ,Oral: genetics ,pathology ,Mouth Mucosa: drug effects ,pathology ,Receptor ,ErbB-2: genetics ,Serine Endopeptidases: physiology ,Serine Proteinase Inhibitors: pharmacology ,Trypsin Inhibitor ,Bowman-Birk Soybean: pharmacology ,biochemical marker ,bowman birk inhibitor ,proteinase ,article ,catalysis ,drug effect ,enzyme activity ,gene expression regulation ,human ,human cell ,human tissue ,hydrolysis ,leukoplakia ,malignant transformation ,mouth mucosa ,oncogene ,priority journal ,protein domain ,Cell Transformation ,Neoplastic ,Cells ,Cultured ,Dose-Response Relationship ,Drug ,Gene Expression Regulation ,Neoplastic ,Humans ,Leukoplakia ,Oral ,Mouth Mucosa ,Receptor ,erbB-2 ,Serine Endopeptidases ,Serine Proteinase Inhibitors ,Trypsin Inhibitor ,Bowman-Birk Soybean - Abstract
The protease catalyzing the hydrolysis of the tripeptide fluorescence substrate, butoxycarbonyl-valine-proline-arginine-(7-amino-4-methylcoumarin) (Boc-Val-Pro-Arg-MCA) and the neu oncogenic protein are potentially useful biomarkers for human cancer prevention studies. In the present study, we standardized a specific substrate hydrolysis method for measuring this protease activity in human oral mucosal cells and characterized the relationship between neu oncogene expression and protease activity in patients enrolled in an oral cancer prevention trial using Bowman Birk Inhibitor Concentrate (BBIC) as the cancer preventive agent. The results demonstrate that changes in the protease activity in oral mucosal cells after BBIC treatment correlated with the changes in the neu protein levels in oral mucosal cells (r = 0.726, P < 0.001) and serum (r = 0.675, P < 0.001), suggesting that the Boc-Val-Pro-Arg-MCA hydrolyzing activity can be as useful as neu oncogene expression as a cancer biomarker. In the 25 patients enrolled in the study, the level of neu protein in oral mucosal cells correlated with the serum neu protein concentration in the patients before BBIC treatment (r = 0.645, P < 0.001). However, such a correlation was not observed after the BBIC treatment, suggesting that BBI may inhibit serine protease(s) involved in the cleavage of neu protein on the cell surface, thereby preventing the release of the extracellular domain of neu protein into the circulation. By inhibiting the cleavage of neu protein on the cell surface, BBI could prevent malignant and premalignant cells expressing high levels of neu protein antigen from escaping host immunological surveillance control. more...
- Published
- 1999