Expression of N-myristoyltransferase inhibitor protein and its relationship to c-Src levels in human colon cancer cell lines

Earlier, we have reported that N-myristoyltransferase (MMT) activity is higher in colonic epithelial neoplasms than in normal appearing colonic tissue and that increase in NMT activity appears at an early stage in colonic carcinogenesis [Magnuson, B., Raju, R, V, S,, Moyana, T. N,, and Sharma, R. K. (1995) J. Natl. Cancer Inst. 87, 1630-1635]. In this study, we demonstrate increased NMT mRNA in well-differentiated adenocarcinomas, NMT and c-Src mRNA levels were generally elevated in a subset of human colon cancer cell lines. Western blotting analysis employing N-myristoyltransferase inhibitory protein (NPP`) antibody demonstrated low levels of NIP71 in high-expressing c-Src cell lines and high levels of NIP71 in low-expressing c-Src cell lines. Interestingly, down regulation of c-Src by antisense expression in the HT-29 cell line resulted in increased expression of NIP71 suggesting c-Src may negatively regulate NPP` expression. Furthermore, this is the first study demonstrating the expression of NIP71 in human colon cancer cell lines and a possible relationship to colon carcinogenesis. (C) 2000 Academic Press.