Survivin expression correlates with apoptosis resistance after lymphocyte activation and is found preferentially in memory T cells

Kornacker, Martin; Verneris, Michael R.; Kornacker, Birgit; Scheffold, Christian; Negrin, Robert S.

doi:10.1016/s0165-2478(01)00186-9

Cited by 52 publications

(49 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inhibitors of apoptosis proteins (IAP) have been shown to be able to inhibit cell apoptosis and have direct effects on caspase-9 and caspase-3. 49 Therefore, we also determined the effects of oridonin treatment on the expression of IAP family members. As shown in Figure 8, oridonin treatment decreased the expression of cIAP1, XIAP and survivin.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Oridonin induced apoptosis through Akt and MAPKs signaling pathways in human osteosarcoma cells

Jin¹,

Shen²,

Wang³

et al. 2007

Cancer Biology & Therapy

View full text Add to dashboard Cite

Previous studies have shown that oridonin, a diterpenoid isolated from Rabdosia rubescens, was able to inhibit proliferation and induce apoptosis in several cell types. But the mechanisms remain poorly understood. In this study, we investigated the apoptosis-inducing effect and mechanisms of action of oridonin in human osteosarcoma cells. Our results demonstrated that oridonin induced concentration-and time-dependent suppression of proliferation and activation of apoptosis in U2OS, MG63 and SaOS-2 osteosarcoma cell lines. Oridonin induced the release of cytochrome c accompanied by activation of caspase-9, caspase-3 and cleavage of poly(ADP-ribose) polymerase (PARP). These events were all inhibited by z-VAD-fmk, a universal inhibitor of caspases. Oridonin treatment dephosphorylated constitutively active AKT, FOXO transcription factor, and glycogen synthase kinase 3 (GSK3). In addition, oridonin decreased the phosphorylation of ERK and increased the phosphorylation of p38 MAPK and JNK. Furthermore, oridonin treatment down-regulated the expression of the inhibitor of apoptosis protein(IAP) in osteosarcoma cells. All together, our results suggested that oridonin is able to inactivate Akt and ERK and activate p38 MAPK and JNK signalling pathways in osteosarcoma cells causing the suppression of proliferation and induction of mitochondria-and caspasedependent apoptosis.

show abstract

Section: Resultsmentioning

confidence: 99%

“…49 IAPs expression is also regulated by MAPKs family. 50,51 It has been demonstrated that IAPs is able to inhibit the activity of caspases and prevent the apoptosis induced by various stimuli.…”

Section: Discussionmentioning

confidence: 99%

Oridonin induced apoptosis through Akt and MAPKs signaling pathways in human osteosarcoma cells

Jin¹,

Shen²,

Wang³

et al. 2007

Cancer Biology & Therapy

View full text Add to dashboard Cite

show abstract

“…Analysis of matched pairs of non-neoplastic and neoplastic tissue samples revealed expression of both survivin variants in nonneoplastic gastric tissues and a significant increase in survivinbut not survivin-DEx3 -mRNA expression levels in cancer tissue. Especially the use of more sensitive RT -PCR has demonstrated survivin expression in other non-neoplastic tissues as well, including normal lung samples, endothelial cells and lymphocytes (Monzo et al, 1999;Tran et al, 1999;Kornacker et al, 2001). The low levels of survivin mRNA in non-neoplastic tissues argue against the assumption that increased survivin levels in gastric cancer might only be due to an increased proportion of lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Expression of different survivin variants in gastric carcinomas: first clues to a role of survivin-2B in tumour progression

et al. 2002

View full text Add to dashboard Cite

Survivin is a novel member of the inhibitor of apoptosis family and determines the susceptibility of tumour cells to proapoptotic stimuli. Recently, we identified two novel alternative splice variants of survivin, differing in their anti-apoptotic properties: whereas the anti-apoptotic potential of survivin-DEx3 is preserved, survivin-2B has lost its anti-apoptotic potential and may act as a naturally occurring antagonist of survivin. Because the in vivo expression of these alternative splice variants has not been explored so far, we analysed gastric carcinomas of different histological subtypes, grades and stages. Since no antibodies are currently available to determine the novel splice variants, quantitative reverse transcriptase polymerase chain reaction was performed, using RNA samples obtained from 30 different gastric carcinomas. Polymerase chain reactions products were quantified by densitometric evaluation. We found that all gastric carcinomas, irrespective of their histological types, grades or stages, express survivin-DEx3, survivin-2B and survivin, the latter being the dominant transcript. Comparing the disease stages I+II with III+IV, expression of survivin and survivin-DEx3 remained unchanged. In contrast, a significant (P=0.033) stage-dependent decrease in the expression of survivin-2B became evident. Our study demonstrates for the first time the expression of alternative splice variants in gastric carcinomas and provides a first clue to a role of survivin-2B in tumour progression.

show abstract

“…Survivin is expressed in thymocytes, splenic T cells, and human adult peripheral blood T lymphocytes, and its expression can be induced by interleukin-2 plus anti-CD3 (29), concanavalin A (7), or phytohemagglutinin (73). The role of survivin in T cells has been extensively investigated using T cell -specific survivin knockout mice (9,27).…”

Section: Role Of Survivin Int Lymphocytesmentioning

confidence: 99%

Survivin, a cancer target with an emerging role in normal adult tissues

Fukuda

Pelus

2006

Molecular Cancer Therapeutics

432

360

View full text Add to dashboard Cite

Survivin, an inhibitor of apoptosis protein, is highly expressed in most cancers and associated with chemotherapy resistance, increased tumor recurrence, and shorter patient survival, making antisurvivin therapy an attractive cancer treatment strategy. However, growing evidence indicates that survivin is expressed in normal adult cells, particularly primitive hematopoietic cells, T lymphocytes, polymorphonuclear neutrophils, and vascular endothelial cells, and may regulate their proliferation or survival. In preclinical animal models, targeted antisurvivin therapies show efficacy without overt toxicity. However, consequences of prolonged survivin disruption in normal cells, particularly those associated with continuous renewal, have not been clearly determined. Understanding the role of survivin in normal versus malignant cells will be important in identifying strategies that maximally disrupt survivin in cancer cells with minimal effect on normal tissues. In this review, we summarize the prognostic relevance of survivin in cancer that justifies the pursuit of antisurvivin therapies and discuss differences in survivin expression between normal and cancer cells. We subsequently review expression of survivin in normal adult tissues and evaluate preclinical antisurvivin therapies reported to date in light of emerging roles for survivin in normal physiology, particularly hematopoiesis, angiogenesis, and immune function. [Mol Cancer Ther 2006;5(5):1087 -98]

show abstract

Survivin expression correlates with apoptosis resistance after lymphocyte activation and is found preferentially in memory T cells

Cited by 52 publications

References 21 publications

Oridonin induced apoptosis through Akt and MAPKs signaling pathways in human osteosarcoma cells

Oridonin induced apoptosis through Akt and MAPKs signaling pathways in human osteosarcoma cells

Expression of different survivin variants in gastric carcinomas: first clues to a role of survivin-2B in tumour progression

Survivin, a cancer target with an emerging role in normal adult tissues

Contact Info

Product

Resources

About