Generation of a Novel Transgenic Mouse Model for Bioluminescent Monitoring of Survivin Gene Activity in Vivo at Various Pathophysiological Processes

Li, Fengzhi; Cheng, Qing; Ling, Xiang; Stablewski, Aimee; Tang, Lei; Foster, Barbara A.; Johnson, Candace S.; Rustum, Youcef M.; Porter, Carl W.

doi:10.2353/ajpath.2010.090414

Cited by 19 publications

(20 citation statements)

References 63 publications

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“…Mortalin, for instance, is constitutively expressed in planarian neoblasts and is necessary both for normal cell turnover and for regeneration (Conte et al, 2009). Survivin is involved in maintenace of stem cell and protects them from apoptosis (Li et al, 2010; Marconi et al, 2007). TCTP is implicated in regulation of pluripotency via control of transcription of oct4 and nanog (Koziol et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Expression of Wnt9, TCTP, and Bmp1/Tll in sea cucumber visceral regeneration

Mashanov

Zueva

García‐Arrarás

2012

Gene Expression Patterns

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We employ non-radioactive in situ hybridization techniques, which combine good tissue morphology preservation with high sensitivity of transcript detection, to map gene expression in the regenerating digestive tube of the sea cucumber Holothuria glaberrima. We investigated localization of transcripts of Wnt9, TCTP, Bmp1/Tll, the genes that have been previously known to be implicated in embryogenesis and cancer. The choice was determined by our long-term goal of trying to understand how the developmental regulatory pathways known to be involved in tumor development can be activated in post-traumatic regeneration without leading to malignant growth. The gene expression data combined with the available morphological information highlight the gut mesothelium (the outer layer of the digestive tube) as a highly dynamic tissue, whose cells undergo remarkable changes in their phenotype and gene expression in response to injury. This reversible transition of the gut mesothelium from a complex specialized tissue to a simple epithelium composed of rapidly proliferating multipotent cells seems to depend on the expression of genes from multiple developmental/cancer-related pathways.

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Section: Discussionmentioning

confidence: 99%

Expression of Wnt9, TCTP, and Bmp1/Tll in sea cucumber visceral regeneration

Mashanov

Zueva

García‐Arrarás

2012

Gene Expression Patterns

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“…In malignant cells, however, there is evidence that beside cell cycle dependent regulation, survivin may be unregulated independently of mitosis [15,16] by a variety of mechanisms. These include amplification of the survivin locus on chromosome 17q25 [17], demethylation of the survivin promoter and exons [18], and increased promoter activity [13].…”

Section: Survivin Structure and Functionmentioning

confidence: 97%

The Role of Survivin for Radiation Oncology: Moving Beyond Apoptosis Inhibition

Rödel

Reichert²,

Sprenger³

et al. 2011

CMC

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Alterations in the expression of apoptosis-related proteins, like the inhibitor of apoptosis (IAP) protein family, display a pivotal pathway by which cancer cells acquire resistance to therapeutic treatment. Among this family, survivin, the smallest and structural unique member, deserves growing attention due to its universal over-expression in human tumors, and its prominent role in disparate networks of cellular division, intracellular signaling and apoptosis. Several preclinical studies have demonstrated that targeting survivin expression by the use of small interfering RNAs, dominant negative mutants, antisense-oligonucleotides and small molecule repressors sensitized tumor cells towards chemotherapy and irradiation and reduced tumor growth potential. Due to these properties, survivin has been proposed as a molecular target for anticancer therapies. Recent studies further revealed that radio-sensitization achieved by survivin inhibition seems to be multifaceted and involves caspase-dependent and caspase-independent mechanisms. In general, an enhanced rate of apoptosis, and pronounced cell cycle arrest have been observed. More recently, a hampered DNA-damage response has been noted, indicating a distinct role of the protein in radiation-induced double strand break repair. These properties were linked to a nuclear import and physical interrelationship with members of the DNA-DSB repair machinery such as phospho-histone H2AX and DNA dependent Protein Kinase (DNA-PKcs). The applicability of survivin-driven strategies in clinical practice is currently under investigation as the first survivin inhibitors successfully entered phase I/II trials. Although these trials do not include radiation therapy at present, survivin inhibitors may represent a novel type of molecular antagonists to improve the effectiveness of radiation therapy or chemoradio-therapy.

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“…This phenotype is exemplified by survivin (6), an IAP with essential roles in cell division and inhibition of apoptosis aberrantly overexpressed in virtually every human tumor in vivo (7). Although it is still unclear which of the two main functions of survivin is predominantly exploited in cancer, evidence from transgenic models points to a pivotal role of survivin cytoprotection in the growth of epithelial (8) and hematopoietic (9) malignancies, potentially via deregulation of stem cell-like compartment(s) in vivo (10).…”

Section: Members Of the Inhibitor Of Apoptosis (Iap)mentioning

confidence: 99%

Developmental Control of Apoptosis by the Immunophilin Aryl Hydrocarbon Receptor-interacting Protein (AIP) Involves Mitochondrial Import of the Survivin Protein

Kang

Xia

Pop

et al. 2011

Journal of Biological Chemistry

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Survivin is a multifunctional protein with essential roles in cell division and inhibition of apoptosis, but the molecular underpinnings of its cytoprotective properties are poorly understood. Here we show that homozygous deletion of the aryl hydrocarbon receptor-interacting protein (AIP), a survivin-associated immunophilin, causes embryonic lethality in mice by embryonic day 13.5-14, increased apoptosis of Ter119 ؊ / CD71؊ early erythropoietic progenitors, and loss of survivin expression in its cytosolic and mitochondrial compartments in vivo. In import assays using recombinant proteins, AIP directly mediated the import of survivin to mitochondria, thus enabling its anti-apoptotic function, whereas a survivin 1-141 mutant that does not bind AIP was not imported to mitochondria and failed to inhibit apoptosis. AIP-directed mitochondrial import of survivin did not affect cell division, was independent of the organelle transmembrane potential, did not require the chaperone Heat Shock Protein 90 (Hsp90), and was inhibited by cytosolic factor(s) present in normal cells. shRNA knockdown of the mitochondrial import receptor Tom20 abolished mitochondrial import of survivin and sensitized tumor cells to apoptosis, whereas silencing of Tom70 had no effect. Therefore, an AIPTom20 recognition contributes to cell survival in development and cancer by mediating the mitochondrial import of survivin.

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Generation of a Novel Transgenic Mouse Model for Bioluminescent Monitoring of Survivin Gene Activity in Vivo at Various Pathophysiological Processes

Cited by 19 publications

References 63 publications

Expression of Wnt9, TCTP, and Bmp1/Tll in sea cucumber visceral regeneration

Expression of Wnt9, TCTP, and Bmp1/Tll in sea cucumber visceral regeneration

The Role of Survivin for Radiation Oncology: Moving Beyond Apoptosis Inhibition

Developmental Control of Apoptosis by the Immunophilin Aryl Hydrocarbon Receptor-interacting Protein (AIP) Involves Mitochondrial Import of the Survivin Protein

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