[Anti-apoptotic potencial role of p38 in prostate cancer]. / Potencial anti-apoptótico de p38 en cáncer de próstata.

INTRODUCTION: 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). MATERIAL AND 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. CONCLUSION: 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.

Potencial anti-apoptótico de p38 en cáncer de próstata / Anti-apoptotic potencial role of P38 in prostate cancer

Introducción: En cáncer de próstata, la vía de señalización intracelular de TNF-α parece estar desviada hacia la activación de p38. p38 podría proteger a las células tumorales de la muerte inducida por TNF-α. Nos propusimos estudiar el papel que desempeña p38 tanto in vivo (evaluando algunos factores activados por p38 en cáncer de próstata), como in vitro (en las líneas celulares tumorales de próstata LNCaP y PC3, tratadas previamente con TNF-α).Material y métodos: Para los estudios in vitro se utilizaron las líneas celulares LNCaP y PC3. Los tratamientos se realizaron con TNF-α (diferentes concentraciones) y el inhibidor específico de p38 (SB203580). El índice apoptótico se evaluó mediante DAPI y citometría de flujo. La activación de p38 se determinó mediante Western blot. Para los estudios in vivo se usaron 15 próstatas normales (PN) y 27 de cáncer (CP) procesadas para inmunohistoquímica y Western blot. Resultados: In vitro, el aumento de la concentración de TNF-α indujo apoptosis en LNCaP, pero no en PC3. El tratamiento con TNF-α produjo un aumento de la fosforilación de p38 en concentraciones intermedias, mientras que enPC3 no se observaron cambios en la activación. El pretratamiento con SB203580 y TNF-α produjo un aumento significativo de la apoptosis en LNCaP. In vivo todos los pacientes con PN resultaron positivos para p-Elk-1 y p-ATF-2 (núcleo de células epiteliales). En CP no sólo aumenta la expresión de estos factores, sino que se localizaron tanto en núcleo como en citoplasma. Conclusión: Nuestros datos in vitro e in vivo sugieren que p38 juega un importante papel en la progresión del cáncerde próstata. Estas observaciones sugieren que tratamientos centrados en el control de la activación de p38 podrían serefectivos en el tratamiento contra el cáncer de próstata (AU)

Introduction: TNF-α transduction pathway in prostate cancer seems to be diverted towards p38 activation. P38 may protect prostate tumoral cells from TNF-α 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-α).Material and methods: Two prostatic tumoral cell lines (LNCaP and PC3) were used in in vitro studies. Two different experiments were made: with TNF-α (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 vivo study, all of them were processed for immunohistochemistry and Western-blot. Results: In vitro, TNF-α induced apoptosis in LnCap when we increased its concentration but not in PC3. TNF-α stimulationled to increase a time-dependent p38 phosphorylation in two intermediate doses where as in PC3 not changes were found. In LNCaP after its preincubation with SB203580 and TNF-α 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. Conclusion: 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 (AU)