Mitogen Activated Protein kinase signal transduction pathways in the prostate

Signal transduction via mitogen activated protein (MAP) kinases plays a key role in a variety of cellular responses, including proliferation, differentiation, and cell death. MAP kinases have provided a focal point for remarkably rapid advances in our understanding of the control of cellular events by growth factors and stresses. Since their initial discovery in yeast, over a dozen MAP kinase families have been identified of these highly genetically conserved proteins. MAP kinase signal transduction pathways have not been studied in great detail in the prostate; however over one hundred publications describing the effects of various manipulations, including growth factors, chemical modifiers and androgens on prostatic cells have been described in the literature. Despite these studies, the structure and function of the MAP kinase pathways in prostate are far from clearly understood.Diseases of the prostate are a tremendous source of morbidity and mortality in aging males. Benign enlargement of the prostate gland is a significant source of discomfort and prostate cancer is the second leading cause of cancer related deaths in males. Most of the prostate cancer deaths result from emergence of an androgen resistant phenotype of prostate cancer. Unfortunately, treatment options for these androgen resistant prostate cancer patients are few and generally ineffective. These facts underline the need to develop new therapies that will improve outlook for hormone-independent prostate cancer. Several lines of evidence suggest a role for MAP kinase signal transduction pathways in prostate cancer. Here we provide a comprehensive review of studies specifically using prostate tissue or cell lines. Admittedly, many more publications may have examined some aspect of MAPKs, but we focused on abstracts including MAPK, ERK, JNK, or p38.The three major MAP kinase (MAPK) pathways include the extracellular-signal regulated kinase (ERK, also known as p42/44 MAP kinase), c-jun N-terminal kina