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 hig her in colonic epithelial neoplasms than in normal appearing colonic tissue and that increase in NMT activity appears at an early stage in colonic car cinogenesis [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 m RNA levels were generally elevated in a subset of human colon cancer cell l ines. Western blotting analysis employing N-myristoyltransferase inhibitory protein (NPP`) antibody demonstrated low levels of NIP71 in high-expressin g c-Src cell lines and high levels of NIP71 in low-expressing c-Src cell li nes. 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 st udy demonstrating the expression of NIP71 in human colon cancer cell lines and a possible relationship to colon carcinogenesis. (C) 2000 Academic Pres s.