PMID- 9010448 OWN - NLM STAT- MEDLINE DCOM- 19970224 LR - 20091119 IS - 0023-6837 (Print) IS - 0023-6837 (Linking) VI - 76 IP - 1 DP - 1997 Jan TI - Mitogen-activated protein kinase phosphatase 1 is overexpressed in prostate cancers and is inversely related to apoptosis. PG - 37-51 AB - Several oncogenes involved in prostate carcinogenesis activate mitogen-activated protein (MAP) kinases, which can relay both proliferative (via extracellular regulated kinases (ERK)) and apoptotic signals (via jun N-terminal protein kinases (JNK)) to the nucleus. Mitogen-activated protein kinase phosphatase 1 (MKP-1) is induced by several oncogenes in the ras-dependent pathway and can inactivate both MAP kinase pathways. The role of MKP-1 in proliferation and apoptosis is, however, still controversial. A series of 51 prostate cancers, including a subset (n = 13) that had been previously treated by androgen ablation, was used to examine whether MKP-1 mRNA and protein expression correlated with that of ERK-1, JNK-1, bcl-2, which confers resistance to apoptosis, and apoptotic index measured by in situ end-labeling of fragmented DNA. In a subset of tumors, MKP-1 expression was assessed by semiquantitative RT-PCR and was compared with both ERK-1 and JNK-1 enzymatic activity. In cases not treated by androgen ablation, MKP-1 was overexpressed in the preinvasive stage of prostate cancer, but its expression decreased with higher histologic grade and advanced disease stage. There was coexpression of MKP-1, ERK-1, and JNK-1 proteins. In addition, MKP-1 expression was inversely correlated to JNK-1 but not to ERK-1 enzymatic activity. Finally, MKP-1 and bcl-2 were inversely related to apoptotic indices. In cases treated by total androgen ablation, MKP-1 and bcl-2 were both down-regulated, whereas JNK-1 was up-regulated. Subpopulations of cells that did not undergo apoptosis maintained expression of both MKP-1 and bcl-2. These results suggest that MKP-1 overexpression is associated with the early phases of neoplastic transformation in prostate tissue. The enzymatic data on MKP-1 kinase substrates and the inverse correlation between MKP-1 and parameters of programmed cell death support the hypothesis that MKP-1 inhibits apoptosis in human prostate tumors, perhaps through the JNK pathway. FAU - Magi-Galluzzi, C AU - Magi-Galluzzi C AD - Department of Pathology, Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA. FAU - Mishra, R AU - Mishra R FAU - Fiorentino, M AU - Fiorentino M FAU - Montironi, R AU - Montironi R FAU - Yao, H AU - Yao H FAU - Capodieci, P AU - Capodieci P FAU - Wishnow, K AU - Wishnow K FAU - Kaplan, I AU - Kaplan I FAU - Stork, P J AU - Stork PJ FAU - Loda, M AU - Loda M LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Lab Invest JT - Laboratory investigation; a journal of technical methods and pathology JID - 0376617 RN - 0 (Cell Cycle Proteins) RN - 0 (Immediate-Early Proteins) RN - 0 (RNA, Messenger) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 3.1.3.16 (Phosphoprotein Phosphatases) RN - EC 3.1.3.16 (Protein Phosphatase 1) RN - EC 3.1.3.48 (DUSP1 protein, human) RN - EC 3.1.3.48 (Dual Specificity Phosphatase 1) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatases) SB - IM MH - *Apoptosis MH - Calcium-Calmodulin-Dependent Protein Kinases/biosynthesis MH - *Cell Cycle Proteins MH - Cell Division MH - Dual Specificity Phosphatase 1 MH - Gene Expression MH - Humans MH - Immediate-Early Proteins/analysis/*biosynthesis MH - Immunohistochemistry MH - In Situ Hybridization MH - JNK Mitogen-Activated Protein Kinases MH - Male MH - Mitogen-Activated Protein Kinase 3 MH - *Mitogen-Activated Protein Kinases MH - *Phosphoprotein Phosphatases MH - Polymerase Chain Reaction MH - Prostate/cytology/*enzymology/pathology MH - Prostatic Hyperplasia/enzymology/pathology MH - Prostatic Neoplasms/*enzymology/*pathology MH - Protein Phosphatase 1 MH - Protein Tyrosine Phosphatases/analysis/*biosynthesis MH - RNA, Messenger/biosynthesis MH - Transcription, Genetic EDAT- 1997/01/01 00:00 MHDA- 1997/01/01 00:01 CRDT- 1997/01/01 00:00 PHST- 1997/01/01 00:00 [pubmed] PHST- 1997/01/01 00:01 [medline] PHST- 1997/01/01 00:00 [entrez] PST - ppublish SO - Lab Invest. 1997 Jan;76(1):37-51.