Regulation of proliferation/apoptosis equilibrium by mitogen-activated protein kinases in normal, hyperplastic, and carcinomatous human prostate

Abstract

This study investigate the expression of the mitogen-activated protein kinases (MAPKs) in normal prostate, benign prostatic hyperplasia (BPH), and prostatic cancer (PC), and also the possible relationship between the activity of these MAPKs and the apoptosis/proliferation index. Immunochemical techniques were carried out using 2 mouse monoclonal antibodies against human extracellular signal-regulated protein kinase (ERK) and Jun N-terminal kinase (JNK), and 1 goat polyclonal antibody against mouse p38. To compare the results obtained in the 3 specimens, the average percentages of both epithelial and stromal immunostained cells were calculated on immunostained sections. For each of the 3 kinases studied, the percentage of immunostained stromal cells did not change with prostatic alterations. For both ERK and p38, the percentage of immunostained epithelial cells increased significantly in BPH and even more so in PC. For JNK, the percentage of immunostained epithelial cells increased significantly only in PC. These results suggest that ERK could be involved in the elevated proliferation indexes reported in BPH and PC, whereas p38 might contribute to the increased apoptotic index reported in PC. The most probable action of JNK in PC would be cell proliferation stimulation. Overexpression of MAPKs, involved in the development of prostatic hyperplasia and neoplasia, might be secondary to the overexpression of several growth factors.