Expression of Inhibitor of Apoptosis Proteins in Small- and Non-Small-Cell Lung Carcinoma Cells

Ekedahl, Jessica; Joseph, Bertrand; Grigoriev, M.; Müller, Malin; Magnusson, Carina; Lewensohn, Rolf; Zhivotovsky, Boris

doi:10.1006/excr.2002.5608

Cited by 46 publications

(32 citation statements)

References 47 publications

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“…3). The latter findings confirm data previously reported for the expression of survivin and XIAP mRNAs in panels of different NSCLC and SCLC cell lines (54,55).…”

Section: Resultssupporting

confidence: 92%

Increased expression of inhibitor of apoptosis proteins, survivin and XIAP, in non-small cell lung carcinoma

Kr̆epela

Dankova²,

Moravcikova³

et al. 2009

Int J Oncol

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Abstract.Members of the inhibitor of apoptosis protein (IAP) family, survivin and X-chromosome-linked IAP (XIAP), contribute to apoptosis resistance of cancer cells, and an increase in their expression may elevate the apoptotic threshold of malignant tumours during their growth and progression. In the present study, we investigated the expression status of survivin and its interactants hepatitis B X-interacting protein (HBXIP) and XIAP in non-small cell lung carcinoma (NSCLC) cell lines and NSCLC tumours and matched lungs from surgically treated patients in relation to their clinicopathological data. The expression of survivin, HBXIP and XIAP mRNAs was quantitated by real-time RT-PCR. The expression of survivin and XIAP proteins was analysed by Western blotting and ELISA. Survivin mRNA and protein levels were highly upregulated in NSCLC cells and tissues as compared to the lungs. In fact, the levels of survivin mRNA and protein in the tumours were more than 10-fold higher in 96 (64%) and 72 (82%) of the 150 and 88 examined NSCLC patients, respectively. The expression of survivin mRNA was higher in squamous cell lung carcinomas than in lung adenocarcinomas (LACs; P=0.003) and in less-differentiated tumours than in well-differentiated ones (P=0.007). The level of survivin protein was higher in stage IB and stage II+III tumours (P=0.049 and P=0.044), than in stage IA tumours. The BIRC5 promoter polymorphism at nucleotide -31 did not influence the expression of survivin mRNA and protein in NSCLC cells and tumours. HBXIP mRNA was abundantly expressed in NSCLC cell lines and NSCLC tumours and lungs, while its level was comparable in the tumours and lungs. The expression of XIAP mRNA in NSCLC cell lines and NSCLC tumours and lungs was not significantly different. However, the expression of XIAP protein was higher in NSCLC tumours, particularly in LACs, as compared to the lungs (P=0.017 and P=0.004). In conclusion, the overexpression of survivin in the majority of NSCLCs together with the abundant or upregulated expression of HBXIP and XIAP suggest that tumours are endowed with resistance against a variety of apoptosis-inducing conditions.

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“…3). The latter findings confirm data previously reported for the expression of survivin and XIAP mRNAs in panels of different NSCLC and SCLC cell lines (54,55).…”

Section: Resultssupporting

confidence: 92%

Increased expression of inhibitor of apoptosis proteins, survivin and XIAP, in non-small cell lung carcinoma

Kr̆epela

Dankova²,

Moravcikova³

et al. 2009

Int J Oncol

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“…The most significant stimulation in c-IAP1 IRES activity occurred following treatment with 50 µM etoposide and 20 µM sodium arsenite. Similar levels of stimulation have been reported for c-IAP1 protein induction in cells following low dose ␥ irradiation and etoposide treatments (Ekedahl et al 2002) and XIAP protein induction in …”

Section: Discussionsupporting

confidence: 83%

“…Thus, it is possible the IRES activity of the c-IAP1 5Ј-UTR is regulated during cellular stress. In support of this, posttranscriptional induction of c-IAP1 synthesis has been reported in non-small-cell carcinoma cells following etoposide treatment (Ekedahl et al 2002). To test if c-IAP1 IRES activity is stimulated during cell stress, 293T cells were treated with different doses of etoposide or sodium arsenite, then transiently transfected with capped, polyadenylated pRL-c-IAP1-FL or pRL-HL dicistronic RNAs.…”

Section: Effect Of Cellular Stress On C-iap1 Ires Activitymentioning

confidence: 86%

“…Also, studies investigating the expression of c-IAP1 mRNA and protein in both cells and tissues have demonstrated c-IAP1 expression may also be posttranscriptionally controlled (Tamm et al 2000;Ekedahl et al 2002). A recent report demonstrated 15-deoxy-⌬ 12,14 -prostaglandin J 2 and laminar fluid shear stress could induce c-IAP1 protein expression in vascular endothelial cells without affecting the intracellular levels of its mRNA (Taba et al 2003).…”

Section: Discussionmentioning

confidence: 99%

“…However, the investigation of the expression of c-IAP1 in a panel of human tumor cell lines has provided evidence to suggest that it may also be posttranscriptionally regulated (Tamm et al 2000). A recent study has demonstrated c-IAP1 protein induction in cells treated with etoposide occurred independently of increases in c-IAP1 mRNA (Ekedahl et al 2002). Thus, c-IAP1 expression may be both transcriptionally and posttranscriptionally regulated, with the latter potentially involving translational regulation and/or protein stability/turnover.…”

Section: Introductionmentioning

confidence: 99%

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Translation of cellular inhibitor of apoptosis protein 1 (c-IAP1) mRNA is IRES mediated and regulated during cell stress

Eden

Byrd²,

Sherrill³

et al. 2004

RNA

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Cellular inhibitor of apoptosis protein 1 (c-IAP1) can regulate apoptosis through its interaction with downstream TNF receptor effectors (TRAF1 and TRAF2), by binding to and inhibiting certain caspases, and by controlling the levels of specific proapoptotic stimuli (e.g., Smac/DIABLO) within the cell. Studies involving the expression of c-IAP1 mRNA and protein in cells and tissues have provided evidence suggesting c-IAP1 expression may be posttranscriptionally controlled. Because the 5-UTR of c-IAP1 mRNA is unusually long, contains multiple upstream AUG codons, and has the potential to form thermodynamically stable secondary structures, we investigated the possibility it contained an internal ribosome entry site (IRES) that may regulate its expression. In the present study, the c-IAP1 5-UTR exhibited IRES activity when dicistronic RNA constructs were translated in rabbit reticulocyte lysate (RRL) and in transiently transfected cells. IRES-mediated translation was similar to that exhibited by the hepatitis C virus IRES but varied significantly in RRL and in HeLa, HepG2, and 293T cells, indicating the c-IAP1 IRES was system and cell type specific. IRES-mediated translation was maintained in mono-and dicistronic constructs in which the UTR was inserted downstream from a stable hairpin that prevented cap-dependent ribosome scanning. In cells, the presence or absence of a methylated cap did not significantly affect the translation of polyadenylated, monocistronic RNAs containing the c-IAP1 5-UTR. IRES-mediated translation was stimulated in transfected cells treated with low doses of pro-apoptotic stimuli (i.e., etoposide and sodium arsenite) that inhibited endogenous cellular translation.

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Apoptosis: why and how does it occur in biology?

Ulukaya

Acılan

Yılmaz³

2011

Cell Biochemistry & Function

189

121

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The literature on apoptosis has grown tremendously in recent years, and the mechanisms that are involved in this programmed cell death pathway have been enlightened. It is now known that apoptosis takes place starting from early development to adult stage for the homeostasis of multicellular organisms, during disease development and in response to different stimuli in many different systems. In this review, we attempted to summarize the current knowledge on the circumstances and the mechanisms that lead to induction of apoptosis, while going over the molecular details of the modulator and mediators of apoptosis as well as drawing the lines between programmed and non-programmed cell death pathways. The review will particularly focus on Bcl-2 family proteins, the role of different caspases in the process of apoptosis, and their inhibitors as well as the importance of apoptosis during different disease states. Understanding the molecular mechanisms involved in apoptosis better will make a big impact on human diseases, particularly cancer, and its management in the clinics.

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Expression of Inhibitor of Apoptosis Proteins in Small- and Non-Small-Cell Lung Carcinoma Cells

Cited by 46 publications

References 47 publications

Increased expression of inhibitor of apoptosis proteins, survivin and XIAP, in non-small cell lung carcinoma

Increased expression of inhibitor of apoptosis proteins, survivin and XIAP, in non-small cell lung carcinoma

Translation of cellular inhibitor of apoptosis protein 1 (c-IAP1) mRNA is IRES mediated and regulated during cell stress

Apoptosis: why and how does it occur in biology?

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