Increased activity of MAP, p70S6 and p90rs kinases is associated with AP-1activation in spontaneous liver tumours, but not in adjacent tissue in mice

Growth factor-responsive protein kinases regulate expression of genes invol ved in cell cycle control, cell proliferation and differentiation. To bette r understand the role of these kinases in the abnormal proliferation of mal ignant cells, we examined basal and epidermal growth factor (EGF)-inducible mitogen-activated protein kinase (MAPK), p70S6k and p90rsk activities in s pontaneous hepatocellular neoplasms (adenomas and carcinomas) from CBA-TG m ice and in L1 sarcoma tumours implanted in livers of BALB/c mice. In sponta neous and implanted hepatic tumours, basal cytoplasmic and nuclear MAPK, p7 0S6k and p90rsk activities were significantly higher compared to the activi ties found in the part of the liver uninvolved by the tumour. Interestingly , the activities of these enzymes in the uninvolved tissue of the livers ha rbouring the tumour were higher compared to the livers from control mice. B asal kinase activities correlated with tumour morphology; they were lower i n adenomas than in carcinomas and sarcomas. in contrast to basal activities , EGF-triggered kinase responses in normal livers and hepatic tumours were indistinguishable. Activating protein-1 (AP-I) DNA-binding activity was det ected in tumours but not in the adjacent tissues. Constitutively activated kinases and AP-1 transcription factor found in hepatic malignancies are rem iniscent of cells activated by EGF, suggesting that EGF and its intracellul ar effecters play a role in these malignancies. (C) 2000 Cancer Research Ca mpaign.