survivin gene expression is negatively regulated by the p53 tumor suppressor gene in non-small cell lung cancer

Nakano, Jun; Huang, Cheng-long; Liu, Dage; Ueno, Masaki; Sumitomo, Shinichi; Yokomise, Hiroyasu

doi:10.3892/ijo.27.5.1215

Cited by 22 publications

(24 citation statements)

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“…Considering the major histopathological types of NSCLC and the degree of their differentiation, the expression of survivin mRNA was significantly higher in SQCLCs as compared to LACs, and significantly higher in the less- differentiated than in the well-differentiated SQCLCs and LACs, respectively. These findings confirm previously reported results (56,57). Although the expression of survivin mRNA in stage IB and stage II+III tumours was higher than in stage IA tumours, this difference did not reach statistical significance.…”

Section: Discussionsupporting

confidence: 81%

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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Section: Discussionsupporting

confidence: 81%

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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“…Published works have shown that survivin can be negatively regulated by wild-type p53 and positively regulated by mutant p53 in many cancer cells (56,57). p53 is also related to regulation of Pgp.…”

Section: Discussionmentioning

confidence: 99%

P-glycoprotein and survivin simultaneously regulate vincristine-induced apoptosis in chronic myeloid leukemia cells

Souza

Vasconcelos²,

Reis³

et al. 2011

Int J Oncol

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Abstract. Overexpression of P-glycoprotein (Pgp/ABCB1) in tumor cells is associated with a classic phenotype of multidrug resistance (MDR). Moreover, some members of the inhibitor of apoptosis protein (IAP) family, such as survivin, contribute to an apoptosis-resistant phenotype, by inhibiting chemotherapyinduced cell death and promoting MDR. By using Western blotting, qRT-PCR, Annexin V and immunofluorescence assays we have demonstrated a relationship between Pgp and survivin in a prior sensitive chronic myeloid leukemia (CML) cell line (K562). A high dose of vincristine induced a concomitant overexpression of Pgp and survivin, which was associated with a low apoptotic index in the K562 cell line. In addition, we observed a cytoplasmic co-localization of Pgp and survivin, suggesting a functional association between these two proteins in apoptosis control by a common mechanism. In summary, our data suggest that Pgp and survivin should be analyzed in aggregate because they may have significant impact on drug resistance in CML cells.

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“…This can partially explain why hyperoxia decreased survivin expression as early as after 12 h of exposure. Besides transcriptional regulation, regulation of survivin can occur at various levels, including protein degradation and intracellular sequestration (17,33,43,48). Whether cav-1 is involved in these levels of regulation requires further exploration.…”

Section: Discussionmentioning

confidence: 99%

Deletion of caveolin-1 protects hyperoxia-induced apoptosis via survivin-mediated pathways

Zhang

Lin

Lee

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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Cell death is a prominent feature in lungs following prolonged hyperoxia. Caveolae are omega-shaped invaginations of the plasma membrane. Caveolin-1 (cav-1), a 22-kDa transmembrane scaffolding protein, is the principal structural component of caveolae. We have recently shown that deletion of cav-1 (cav-1 Ϫ/Ϫ ) protected against hyperoxia-induced cell death and lung injury both in vitro and in vivo; however, the mechanisms remain unclear. Survivin, a member of the inhibitor of apoptosis protein family, inhibits apoptosis in tumor cells. Although emerging evidence suggests that survivin is involved in wound healing, especially in vascular injuries, its role in hyperoxia-induced lung injury has not been investigated. Our current data demonstrated that hyperoxia induced apoptosis via suppressing survivin expression. Deletion of cav-1 abolished this suppression and subsequently protected against hyperoxia-induced apoptosis. Using "gain" and "loss" of function assays, we determined that survivin protected lung cells from hyperoxia-induced apoptosis via the inhibition of apoptosis executor caspase-3. Overexpression of survivin by deletion of cav-1 was regulated by Egr-1. Egr-1 functioned as a negative regulator of survivin expression. Deletion of cav-1 upregulated survivin via decreased Egr-1 binding of the survivin promoter region. Together, this study illustrates the effect of hyperoxia on survivin expression and the role of survivin in hyperoxia-induced apoptosis. We also demonstrate that deletion of cav-1 protects hyperoxia-induced apoptosis via modulation of survivin expression.caspase-3; Egr-1 ACUTE LUNG INJURY (ALI) and its more severe manifestation, acute respiratory distress syndrome (ARDS), are devastating conditions that account for high morbidity and mortality among critically ill patients (28, 44). Exposure to high O 2 tension (hyperoxia) has been shown in animal models to induce lung injury that closely resembles ARDS. Hyperoxia triggers an extensive inflammatory response in the lung that is typically followed by severe damage of the alveolar-capillary barrier. This damage results in impaired gas exchange and pulmonary edema (10,30,47). Cell death of pulmonary capillary endothelial cells and alveolar epithelial cells is the major pathological change in hyperoxia-injured lungs (1,13,14,26). Compromised epithelial and endothelial cell function leads to fluid and macromolecule accumulation in the air space and can cause clinical respiratory failure and death (1,13,14,26,47).Address for reprint requests and other correspondence: Y. Jin, Division of Pulmonary, Allergy, and Critical Care Medicine, Dept. of Medicine, Univ. of Pittsburgh, MUH 628NW, 3459 5th Ave., Pittsburgh, PA 15213 (e-mail: jiny@upmc.edu). Fig. 1. Deletion of caveolin-1 (cav-1) protected hyperoxia-induced apoptosis. Cells were treated with hyperoxia (time course), and caspase-3 activity was measured as described in MATERIALS AND METHODS. A: wild-type and cav-1 Ϫ/Ϫ fibroblasts were exposed to hyperoxia. Caspase-3 activity was measured. A time c...

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survivin gene expression is negatively regulated by the p53 tumor suppressor gene in non-small cell lung cancer

Cited by 22 publications

References 0 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

P-glycoprotein and survivin simultaneously regulate vincristine-induced apoptosis in chronic myeloid leukemia cells

Deletion of caveolin-1 protects hyperoxia-induced apoptosis via survivin-mediated pathways

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