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Stage-specific Increases in Cathepsin B Messenger RNA Content in Human Colorectal Carcinoma¹

Departments of Pathology [M. J. M., K. S., M. O., S. S.] and Biochemistry [M. J. M.], Mallory Institute of Pathology [M. J. M., K. S., S. S.], Boston University School of Medicine, Boston, Massachusetts 02118

Cathepsin B mRNA levels and banding patterns were characterized in human colorectal mucosa and carcinoma tissues from patients with tumors of different Dukes' stages. Quantitation of mRNA content using slot blot hybridization demonstrated an increase in cathepsin B message in seven of eight tumor tissues with an average increase of 3.5-fold over patient-matched control mucosa samples. This tumor-specific increase in cathepsin B mRNA confirms and extends our previous observation that cathepsin B enzyme specific activity levels are significantly elevated in colorectal carcinomas. In fact, the increase in mRNA levels is greater and more consistent than the observed increase in enzyme activity, suggesting that posttranscriptional or posttranslational regulation of cathepsin B expression occurs in colorectal tumors. The mRNA data also support our earlier observation that cathepsin B enzyme activity levels are inversely correlated with Dukes' stage. The tumor-specific increase in cathepsin B mRNA content is almost 4 times greater in earlier stage (Dukes' A and B) tumors than in later stage (Dukes' C and D) tumors. Thus, increased cathepsin B gene expression is particularly characteristic of tumors which are in the process of invading the bowel wall or local tissues compared with tumors which have already spread to more distant sites. Northern blot data on cancer/normal pairs indicate that the increase in cathepsin B mRNA in colorectal carcinoma is due primarily to changes in the amount of the 2.2- and 4.0-kilobase transcripts which are seen in control tissue. However, low levels of two additional cathepsin B mRNA transcripts (1.5 and 3 kilobases in size) were also observed in tumor tissue.

¹ This work was supported in part by American Cancer Society Grants PDT-349 and IN-97 and by a William Stokes Award (R.C.P.I.).

² To whom requests for reprints should be addressed, at Department of Pathology, L804, Boston University School of Medicine, 80 E. Concord St., Boston, MA 02118.

Received 8/22/90. Accepted 11/29/90.

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