Regulation of proliferation/apoptosis equilibrium by map kinases in normal, hyperplastic and carcinomatous human prostate

M Royuela, PhD,MI Arenas, PhD, M Ricote, J Alfaro, MVT Lobo, MD, R Vera, MD, B Fraile PhD and R Paniagua PhD

University of Alcala, Alcala de Henares, Madrid Spain

AIMS: To correlate the expression of MAPKs (p38, ERK, JNK) with the malignancy of human prostatic pathologies. METHODS: Biopsies from 15 normal (NP), 25 hyperplastic (BPH) and 25 carcinomatous (PC) human prostates were processed by immunochemical techniques (Western blot and immunohistochemistry) for the detection of MAPKs. A histologic comparative quantification of immunolabelling density also was performed for each antibody with an automatic image analyser (MIP version 4.4, Consulting Image Digital, Barcelona, Spain). RESULTS: For each of the three 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 in PC. For JNK the percentage of immnostained epithelial cells only increased significantly in PC. CONCLUSIONS: In prostate cancer, the overexpression of MAPKs might be secondary to overexpression of some growth factors and, subsequently, MAPKs also might be involved in the development of prostatic hyperplasia and neoplasia. In order to search a dominant target for therapy, it should be taken into account that prostate cancer is a heterogeneous disease in which different growth factors, cytokines, oncogenes or other mitogenic signals may be involved in the uncontrolled apoptosis/cell proliferation, and only when all these factors become well known, a positive therapy could be found.

KEY WORDS: prostate, MAPKs, p38, .

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Novel Therapies, Part 1.