N-Myristoyltransferase overexpression in human colorectal adenocarcinomas

Modification of proteins by myristoylation has been proposed as a chemotherapeutic target against colon cancer because it is important in the function of various signal transduction proteins. Recently we reported that the enzyme that catalyzes this modification, N-myristoyltransferase (NMT), is elevated in colorectal adenocarcinomas [Magnuson, B. A., Raju, R. V. S., Moyana, T. N., and Sharma, R. K. (1995) J. Natl. Cancer. Inst. 87, 1630-1635]. The purpose of the present study was to investigate whether the elevated activity of NMT in colorectal adenocarcinomas is due to an increase in the production of NMT or a change in the structure of the preexisting enzyme. The expression of NMT in normal colonic mucosa and adenocarcinomas from human colorectal surgical specimens was studied by immunoblotting, and its localization was confirmed by immunohistochemistry. The molecular weight of NMT was determined by fast protein liquid chromatography. In both normal mucosa and colorectal adenocarcinomas, NMT with a molecular mass of 48.5 kDa was identified with anti-human NMT and anti-peptide antibody. However, the expression of NMT was found to be higher in the colorectal tumors. This finding was further confirmed by immunohistochemical studies which showed stronger cytoplasmic staining in the tumors. These findings represent the first description of NMT overexpression in colorectal adenocarcinomas. This has implications with regard to (i) the design of chemotherapeutic drugs and (ii) prognosis, for instance, in monitoring colorectal cancer recurrence or metastases.