MAPK ACTIVITY IS DOWN-REGULATED IN HUMAN COLON ADENOCARCINOMA - CORRELATION WITH PKC ACTIVITY

Cellular growth is regulated by a cascade of kinases, among which mito gen activated protein kinase (MAPK) is an integral member of the Ras-m ediated pathway, while protein kinase C (PKC) is recognized as the int racellular receptor of tumor promoters. To assess the role of these tw o signal transduction enzymes in colonic carcinogenesis, we measured M APK and PKC activities in cytosol and membrane compartments of: 1) nor mal colon, 2) colon adenocarcinoma, and 3) histologically normal colon ic tissue taken from the margin of resection of neoplastic colon. Both MAPK and PKC activities were down-regulated in solubilized membranes from the cancers. MAPK activity was also down-regulated in the tissue adjacent to the cancer and designated as histologically normal (by rou tine histopathology). Therefore, MAPK activity appears to be more suit able than PKC as a marker for early detection of colonic transformatio n.