C-Jun N-terminal kinase is required for phorbol ester- and thapsigargin-induced apoptosis in the androgen responsive prostate cancer cell line LNCaP

Androgen signaling and its interactions with other signaling pathways in prostate cancer

“…(69) Similar to other tissues, there is very good correlation between JNK activation and apoptosis in prostate cancer cells; in fact, JNK activation is required for apoptosis induced by various agents in prostate cancer cells in vitro. (70,71) (Lorenzo and Saatcioglu, unpublished data) Consistently, androgen inhibition of apoptosis in prostate cancer cells coincides with inhibition of JNK activation (Lorenzo and Saatcioglu, unpublished data). However, there are also findings that imply that JNK activation may have a role in proliferation of prostate cancer cells.…”

JNK interacting protein 1 (JIP-1) protects LNCaP prostate cancer cells from growth arrest and apoptosis mediated by 12-0-tetradecanoylphorbol-13-acetate (TPA)

“…Further studies using the JNK inhibitor SP600125 confirmed the importance of the JNK/cJun/AP-1 signal pathway in TPA-induced growth arrest of LNCaP cells; SP600125 protected LNCaP cells from TPA-induced growth arrest. Recently, other investigators also reported the contribution of the JNK/c-Jun signaling to TPA-mediated apoptosis of LNCaP cells (Engedal et al, 2002); they transiently transfected JBD of JIP-1 in LNCaP cells to inhibit the JNK/c-Jun signal pathway. These transiently transfected cells were relatively resistant to TPAinduced apoptosis compared to untransfected control cells.…”

Protein kinase Cɛ interacts with Bax and promotes survival of human prostate cancer cells

“…Studies have shown that when LNCaP cells are treated with PMA, there is a rapid and sequential activation of Rb and transcriptional repression of c-myc that precedes the onset of apoptosis (Zhao and Day, 2001). More recently, it was reported that JNK activity is activated by PMA and that LNCaP cells overexpressing the JNK inhibitory protein (JIP) are resistant to PMA-induced apoptosis (Engedal et al, 2002). These data suggest that Rb and JNK may play important roles downstream of PKCa/PKCd in one or more of the mitochondrial-dependent apoptotic pathways that LNCaP cells possess.…”

“…As documented in these and other studies, PMA is a protein kinase C (PKC) agonist that selectively activates a mitochondrial-dependent pathway in the androgen-sensitive lymph node CaP (LNCaP) but not AI (DU145 and PC3) CaP cell lines. Additional examples of agents that preferentially induce cell death in the LNCaP model of early CaP include tumor necrosis factor-alpha (TNFalpha), bryostatin 1, thapsigargin, N-(4-hydroxyphenyl)retinamide, and inhibitors of phosphatidylinositol-3 0 -kinase (PI3-K) (Chen et al, 1999;Gschwend et al, 2000;Murillo et al, 2001;Dhanalakshmi et al, 2002;Engedal et al, 2002). Thus, recurrent CaP cells tend to be extremely resistant to the apoptogenic signals triggered by diverse agents.…”

“…However, PMA-induced production of ceramide appears to preferentially induce necrosis, rather than apoptosis, in LNCaP cells (Engedal and Saatcioglu, 2001). Alternative explanations for the PKC-mediated apoptosis of LNCaP cells have emphasized the possible involvement of the c-myc oncogene (Zhao and Day, 2001) and c-Jun N-terminal kinase (JNK; Engedal et al, 2002). Studies have shown that when LNCaP cells are treated with PMA, there is a rapid and sequential activation of Rb and transcriptional repression of c-myc that precedes the onset of apoptosis (Zhao and Day, 2001).…”