[Anti-apoptotic potencial role of p38 in prostate cancer].
BACKGROUND
TNF-alpha transduction pathway in prostate cancer seems to be diverted towards p38 activation. P38 may protect prostate tumoral cells from TNF-alpha apoptosis induced. The aim of this study was study the role of p38 in vivo (were evaluated some p38 downstream factors), as well as in vitro (in prostatic tumoral cell lines, LNCaP and PC3, pre-treated with TNF-alpha).


METHODS
Two prostatic tumoral cell lines (LNCaP and PC3) were used in in vitro studies. Two different experiments were made: with TNF-alpha (several concentrations) and p38 specific inhibitor (SB203580). The apoptotic index were evaluated using DAPI staining and flow cytometry. P38 activation was measured by Western blot analysis. 15 normal samples (NP) and 27 prostate cancer samples (PC) were used in in vivo study, all of them were processed for immunohistochemistry and Western-blot.


RESULTS
In vitro, TNF-alpha induced apoptosis in LnCap when we increased its concentration but not in PC3. TNF-alpha stimulation led to increase a time-dependent p38 phosphorylation in two intermediate doses whereas in PC3 not changes were found. In LNCaP after its preincubation with SB203580 and TNF-alpha treatment showed a significative increasing of apoptosis. In vivo, all NP samples were found positives to p-Elk-1 and p-ATF-2 (nuclei of epithelial cells). In PC the expression of p-Elk-1 or p-ATF-2 increased and was located in the nucleus and cytoplasm of epithelial cells.


CONCLUSIONS
Our data in vitro and in vivo suggest that p38 plays a very important role in prostatic tumour progression. These data suggest that the control activation of p38 might be a possible target to cancer prostate treatment.
Ricote Belinchón
M
M
Departamento de Biología Celular y Genetica, Universidad de Alcalá, Madrid.
Bethencourt Codes
F R
FR
García-Tuñón Llanio
I
I
Fraile Láiz
B
B
Fernández Sáez
C
C
Aller Tresguerres
P
P
González-García
J
J
Vera San Martín
R
R
Paniagua Gómez-Alvarez
R
R
Royuela García
M
M
D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D045744:Cell Line, Tumor / Q000201:enzymology / Q000473:pathology*; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases