A Role for Survivin in Radioresistance of Pancreatic Cancer Cells

Asanuma, Koichi; Kobayashi, Daisuke; Furuya, Daisuke; Tsuji, Naoki; Yagihashi, Atsuhito; Watanabe, Naoki

doi:10.1111/j.1349-7006.2002.tb02483.x

Cited by 80 publications

(50 citation statements)

References 22 publications

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“…20 Survivin expression is correlated with clinical progression, 58,59 and resistance to chemo-and radiotherapy. 60 A possible mechanism of enhanced tumor survival with high levels of survivin has been suggested to involve modulation of the apoptosis pathway, 61,62 and may depend on inhibition of the two early apoptotic enzymes caspase-3 and caspase-7, 63 thus preventing programmed cell death. This mechanism is supported by the observation that downregulation of survivin expression by induction of the effector cell protease receptor-1 (EPR-1) enhances apoptosis, reduces Comparison of the survivin promoter activity with the EGP-2 promoter activity in primary melanoma cells.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of tumor-specific promoter activities in melanoma

Makhija

Nettelbeck

et al. 2005

Gene Ther

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Gene therapy is a novel therapy for melanoma. To date, however, there is still no powerful tumor specific promoter (TSP) to restrict the transgene expression in melanoma cells. In order to define a useful TSP for targeting in the context of melanoma gene therapy, four promoters, the cyclooxygenase-2 (Cox-2), a-chemokine SDF-1 receptor (CXCR4), epithelial glycoprotein 2 (EGP-2), and survivin, were tested in both established melanoma cell lines and primary melanoma cells. We employed recombinant adenoviral vectors (reAds) each with a candidate TSP (the Cox-2, CXCR4, EGP-2, or survivin), a reporter luciferase gene, and a poly-A signal, all of which were inserted into the E1-deleted region. A reAdGL3Bcytomegalovirus (CMV), containing the CMV promoter and luciferase gene, was used as a positive control to normalize the luciferase activity. Luciferase activity was measured in multiple tumor cell lines and two primary melanoma cell cultures after infection with reAds. Human epithelial melanocytes, HEM, were used as normal control. In contrast to three other promoters, the survivin promoter exhibited the highest activities within both melanoma cell lines and primary melanoma cells, but not in HEMs. Additionally, the survivin promoter exhibited very low activities in major mouse organs including the liver, in vivo. EGP-2 is not active in melanoma; messenger RNA expressions were correlated to promoter activities both in melanoma cell lines and primary cell cultures. Thus, these data suggest that the survivin promoter achieved a 'tumor-on/ liver-off' profile, and thus represents a potentially useful tumor-specific promoter with applications for transcriptional targeting of Ad vector-based cancer gene therapy or oncolysis to melanoma. Gene Therapy (2005) 12, 330-338.

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Section: Discussionmentioning

confidence: 99%

Evaluation of tumor-specific promoter activities in melanoma

Makhija

Nettelbeck

et al. 2005

Gene Ther

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“…Recently, the survivin gene has been described as being selectively expressed in some of the most common human neoplasms as described above, and survivin expression is correlated with clinical progression, 28,29 and resistance to chemo-and radiotherapy. 30 A possible mechanism of enhanced tumor survival with high levels of survivin has been suggested to involve modulation of the apoptosis pathway, 31,32 and may depend on inhibition of the two early apoptotic enzymes caspase-3 and caspase-7, 33 thus preventing programmed cell death. This mechanism is supported by the observation that downregulation of survivin expression by induction of the effector cell protease receptor-1 (EPR-1) enhances apoptosis, reduces tumor growth potential, and results in an increased sensitivity to anticancer agents.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional targeting of tumors with a novel tumor-specific survivin promoter

Zhu

Makhija

et al. 2004

Cancer Gene Ther

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It has been demonstrated that survivin, a novel member of the inhibitor of apoptosis (IAP) protein family, is expressed in human cancers but is undetectable in normal differentiated tissues. We employed a recombinant adenoviral vector (reAdGL3BSurvivin) in which a tumor-specific survivin promoter and a luciferase reporter gene were inserted into the E1-deleted region of adenovirus vector. Luciferase activity was measured in both multiple tumor cell lines and two primary melanoma cells infected with reAdGL3BSurvivin. Human fibroblast and mammary epithelial cell lines were used as negative controls. A reAdGL3CMV, containing the CMV promoter and luciferase gene, was used as a positive control to normalize the luciferase activity generated by the survivin promoter. Our data revealed that the survivin promoter showed high activity in both established tumor cell lines and the primary melanoma cells. In contrast, the in vivo studies indicated that the activities of survivin promoter were extremely low in the major mouse organs. The survivin promoter appears to be a promising tumor-specific promoter exhibiting a ''tumor on'' and ''liver off'' profile, and therefore, it may prove to be a good candidate for transcriptional targeting of cancer gene therapy in a wide variety of tumors.

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“…[12][13][14][15] Its upregulation in human cancer cells has been related to the resistance of the cancer cells to chemoand radiotherapy. 16,17 Furthermore, the level of survivin expression in tumor tissues is correlated with the prognosis of the patients. 15,18,19 These results have provided the rationale of targeting survivin for cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

Tumor-specific gene expression using the survivin promoter is further increased by hypoxia

Yang

Cao

et al. 2004

Gene Ther

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Increasing evidence indicates that survivin, an inhibitor of apoptosis protein (IAP), is expressed in human cancer cells but is absent from most normal adult tissues. Here, we examined the feasibility of using a survivin promoter (Sur-P) to direct therapeutic expression of a proapoptotic gene specifically in human tumor cells. First, we demonstrated that this promoter was highly active in human tumor cells but not in normal cells. Second, we found that Sur-P activity was upregulated by hypoxia in tumor cells. Third, to further enhance this promoter's activity under hypoxia, we added a hypoxia-responsive element (HRE) from the vascular endothelial growth factor gene promoter in its 5 0 region, and showed that this combination resulted in a further increase in the level of gene expression in hypoxic tumor cells. Finally, we demonstrated that expression of an autocatalytic reverse caspase-3 gene by this promoter specifically induced apoptotic cell death in human tumor cells but not in normal cells. These findings support the use of promoters Sur-P or chimeric HRE-Sur-P for generating novel vectors for cancer gene therapy.

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A Role for Survivin in Radioresistance of Pancreatic Cancer Cells

Cited by 80 publications

References 22 publications

Evaluation of tumor-specific promoter activities in melanoma

Evaluation of tumor-specific promoter activities in melanoma

Transcriptional targeting of tumors with a novel tumor-specific survivin promoter

Tumor-specific gene expression using the survivin promoter is further increased by hypoxia

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