PMID- 12913698
OWN - NLM
STAT- MEDLINE
DCOM- 20030926
LR  - 20111102
IS  - 0022-5347 (Print)
IS  - 0022-5347 (Linking)
VI  - 170
IP  - 3
DP  - 2003 Sep
TI  - Pro-apoptotic tumor necrosis factor-alpha transduction pathway in normal 
      prostate, benign prostatic hyperplasia and prostatic carcinoma.
PG  - 787-90
AB  - PURPOSE: Tumor necrosis factor-alpha (TNF-alpha) exerts apoptosis throughout an 
      intracellular transduction pathway that involves the protein kinases TRAF-2 
      (integration point of apoptotic and survival signals), signal regulating kinase 
      (ASK-1) (pro-apoptotic protein), mitogen activated protein kinase-kinase 4 
      (MEK-4) (p38 activator and metastasis suppressor gene), Jun N-terminal kinase 
      (JNK) (stress mitogen activated protein kinase) and the transcription factor 
      activator protein-1 (AP-1). MATERIALS AND METHODS: Biopsies from 20 normal, 35 
      hyperplastic and 27 carcinomatous human prostates were obtained for 
      immunohistochemical and Western blot studies of the mentioned TNF-alpha/AP-1 
      transduction pathway members. RESULTS: In normal prostates immunoreactions to 
      TRAF-2, ASK-1, MEK-4 and JNK were positive, while no immunoreaction to AP-1 was 
      detected. Although in benign prostatic hyperplasia the percent of immunostained 
      specimens and intensity of immunoreactions to TRAF-2, ASK-1, MEK-4 and JNK 
      decreased, the immunoreaction to AP-1 was positive in 27.3%. In most 
      carcinomatous specimens the immune reaction was negative for all proteins of the 
      TRAF-2/AP-1 pathway. CONCLUSIONS: The TNF-alpha/AP-1 pathway might be a response 
      to the excessive proliferative stimulus, although this response seems to be 
      insufficient to counteract extracellular signals of cell proliferation. In 
      prostate cancer this pathway is probably inactivated by other factors, such as 
      p21 (at the ASK-1 level) or bcl-2 (at the JNK level).
FAU - Ricote, Monica
AU  - Ricote M
AD  - Department of Cell Biology and Genetics, University of Alcala, E-28871 Alcala de 
      Henares, Madrid, Spain.
FAU - Royuela, Mar
AU  - Royuela M
FAU - Garcia-Tunon, Ignacio
AU  - Garcia-Tunon I
FAU - Bethencourt, Fermin R
AU  - Bethencourt FR
FAU - Paniagua, Ricardo
AU  - Paniagua R
FAU - Fraile, Benito
AU  - Fraile B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Urol
JT  - The Journal of urology
JID - 0376374
RN  - 0 (Actins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 4)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinases)
RN  - EC 2.7.11.25 (MAP3K4 protein, human)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
SB  - IM
MH  - Actins/metabolism
MH  - Aged
MH  - Aged, 80 and over
MH  - Apoptosis
MH  - Blotting, Western
MH  - Cell Cycle Proteins/metabolism
MH  - Enzyme Activation
MH  - Humans
MH  - Immunohistochemistry
MH  - *JNK Mitogen-Activated Protein Kinases
MH  - MAP Kinase Kinase 4
MH  - MAP Kinase Kinase Kinase 4
MH  - MAP Kinase Kinase Kinases/metabolism
MH  - Male
MH  - Middle Aged
MH  - Mitogen-Activated Protein Kinase Kinases/metabolism
MH  - Prostate/*metabolism
MH  - Prostatic Hyperplasia/*metabolism
MH  - Prostatic Neoplasms/*metabolism
MH  - Signal Transduction/*physiology
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 2003/08/13 05:00
MHDA- 2003/09/27 05:00
CRDT- 2003/08/13 05:00
PHST- 2003/08/13 05:00 [pubmed]
PHST- 2003/09/27 05:00 [medline]
PHST- 2003/08/13 05:00 [entrez]
AID - S0022-5347(05)63231-4 [pii]
AID - 10.1097/01.ju.0000082712.41945.17 [doi]
PST - ppublish
SO  - J Urol. 2003 Sep;170(3):787-90. doi: 10.1097/01.ju.0000082712.41945.17.