Effects of the RAF/MEK/ERK and PI3K/AKT signal transduction pathways on the abrogation of cytokine-dependence and prevention of apoptosis in hematopoietic cells

Shelton, John G.; Steelman, Linda S.; Lee, John Tayu; Knapp, Steven L.; Blalock, William L.; Moye, Phillip W.; Franklin, Richard A.; Pohnert, Steven C.; Mirza, Amer M.; McMahon, Martin; McCubrey, James A.

doi:10.1038/sj.onc.1206321

Cited by 93 publications

(112 citation statements)

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“…It seems that the ability of a cell to die or survive is decided by a critical balance between the ERK pathway and the p38 MAPK or JNK pathway. Deprivation of neurotrophic factors or UV irradiation not only activates stress kinase cascades but also leads to dramatic inhibition of the ERK pathway (13). Furthermore, ERK expression in NIH 3T3 cells impairs the majority of the UV-induced apoptotic response (14).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, deprivation of neurotrophic factors or UV irradiation not only activates stress kinase cascades but also leads to dramatic inhibition of the ERK pathway (12). In addition, ERK is required for survival signaling in response to cellular growth factors (13). Furthermore, overexpression of ERK in NIH 3T3 cells largely impairs the UV-induced apoptotic response (14).…”

Section: Introductionmentioning

confidence: 99%

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Activation of p38 Mitogen-Activated Protein Kinase Is Required for Death Receptor–Independent Caspase-8 Activation and Cell Death in Response to Sphingosine

Yoon

Kim

Park

et al. 2009

Molecular Cancer Research

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Sphingosine induces activation of multiple signaling pathways that play critical roles in controlling cell death. However, the precise molecular mechanism of cell death induced by sphingosine remains to be clarified. In this study, we show that sphingosine induces death receptor -independent caspase-8 activation and apoptotic cell death via p38 mitogen-activated protein kinase (MAPK) activation and that suppression of the MAPK/extracellular signal -regulated kinase (ERK) kinase/ERK pathway by protein phosphatase 2A (PP2A) is required for p38 MAPK activation. Treatment of cells with sphingosine induced suppression of ERK and activation of p38 MAPK. Inhibition of p38 MAPK led to the marked suppression of death receptor -independent caspase-8 activation and subsequent cell death induced by sphingosine. Interestingly, pretreatment with phorbol 12-myristate 13-acetate or transfection of MAPK/ERK kinase/ERK resulting in ERK activation completely attenuated sphingosine-induced p38 MAPK activation. PP2A activity was additionally elevated on sphingosine treatment. Small interfering RNA targeting of PP2A effectively attenuated sphingosine-induced p38 MAPK activation through restoration of ERK activity, suggesting PP2A-mediated opposing regulation of ERK and p38 MAPK. Our findings clearly imply that activation of p38 MAPK promotes death receptor -independent activation of caspase-8 and apoptotic cell death pathways, thus providing a novel cellular mechanism for the anticancer activity of sphingolipid metabolites.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Activation of p38 Mitogen-Activated Protein Kinase Is Required for Death Receptor–Independent Caspase-8 Activation and Cell Death in Response to Sphingosine

Yoon

Kim

Park

et al. 2009

Molecular Cancer Research

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“…As we previously reported, 10 Amol/L angiotensin II stimulated the cell growth of prostate cancer cells in LNCaP and DU145 cells (14). Akt has been implicated in the regulation of a variety of signal transduction pathways, including those involved in cell proliferation (9,(21)(22)(23). To confirm the activation of Akt in LNCaP cells treated with angiotensin II, we did a time-course Western blot analysis.…”

Section: Time Courses Of Akt Phosphorylationmentioning

confidence: 99%

Angiotensin II Induces Oxidative Stress in Prostate Cancer

Uemura

Ishiguro

et al. 2008

Molecular Cancer Research

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Angiotensin II has been shown to be a cytokine especially acting as a growth factor. A local renin-angiotensin system has been identified in the prostate gland, and the physiologic function of angiotensin II seems to be similar in prostate cancer, as we previously reported. In the present study, we explored the biological role of angiotensin II in oxidative stress of prostate cancer cells. Activated Akt was determined, and the expression of oxidative stress-related proteins (p47phox, manganese superoxide dismutase 2, glutathione peroxidase) was examined by Western blotting in LNCaP cells, which were stimulated with angiotensin II and/or an angiotensin II receptor type 1 blocker, candesartan. To examine DNA damage induced by angiotensin II, 8-hydroxy-2 ¶-deoxyguanosine was determined, and Western blots were analyzed to detect checkpoint proteins including p53, Chk2, and cdc2. Immunocytochemical studies of inducible nitric oxide synthase and superoxide anion radical (O 2 À ) were done in LNCaP cells stimulated with angiotensin II. The phosphorylation of Akt was induced by angiotensin II treatment and inhibited by candesartan, as well as by LY294002, an inhibitor of phosphoinositide 3-kinase. Oxidative stress-related proteins were up-regulated by angiotensin II and inhibited by pretreatment with candesartan or catalase. The level of 8-hydroxy-2 ¶-deoxyguanosine was increased by angiotensin II and conversely decreased by candesartan. Immunocytochemical studies showed that angiotensin II enhanced an inflammatory marker, inducible nitric oxide synthase, and the production of O 2 À radical. The hypothesis that angiotensin II has the potential to induce oxidative stress, which may be implicated in carcinogenesis of the prostate gland through long-term exposure to chronic inflammation is proposed. (Mol Cancer Res 2008;6(2):250 -8)

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“…33,34 Infection of cells with retroviral vectors FL5.12 and FL/Doxo cells were infected with retroviral vectors encoding WT or DN p53, constitutively active (CA) (DStuI-MEK-LIDEMANE) or DN MEK1 (MEKLIDA) or an empty retroviral vector (pLXSN), as previously described. [36][37][38] Stably infected (WT and DN p53-and pLXSN-transduced) cells were selected with IL-3 þ 2 mg ml À1 G418 (Geneticin, Invitrogen). 34 Stably infected (DN and CA MEK1, BRAF(WT):ER* and BRAF(V600E): ER*) cells were selected with IL-3 þ 2 mg ml À1 puromycin (Sigma-Aldrich).…”

Section: Limiting Dilution Analysis In Doxorubicinmentioning

confidence: 99%