Expression of survivin is correlated with cancer cell apoptosis and is involved in the development of human pancreatic duct cell tumors

Satoh, Kennichi; Kaneko, Kenzo; Hirota, Morihisa; Masamune, Atsushi; Satoh, Akihiko; Shimosegawa, Tooru

doi:10.1002/1097-0142(20010715)92:2<271::aid-cncr1319>3.0.co;2-0

Cited by 247 publications

(177 citation statements)

References 12 publications

(25 reference statements)

Supporting

Mentioning

159

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, this tumour is usually resistant to conventional chemotherapy and radiation therapy. The pathogenic mechanisms that regulate this aggressive growth behavior of PDC still is to be clarified (Satoh et al, 2001).…”

mentioning

confidence: 99%

Nuclear and cytoplasmic expression of survivin in 67 surgically resected pancreatic cancer patients

et al. 2005

View full text Add to dashboard Cite

Pancreatic cancer is one of the most aggressive gastrointestinal cancer with less than 10% long-term survivors. The apoptotic pathway deregulation is a postulated mechanism of carcinogenesis of this tumour. The present study investigated the prognostic role of apoptosis and apoptosis-involved proteins in a series of surgically resected pancreatic cancer patients. All patients affected by pancreatic adenocarcinoma and treated with surgical resection from 1988 to 2003 were considered for the study. Patients' clinical data and pathological tumour features were recorded. Survivin and Cox-2 expression were evaluated by immunohistochemical staining. Apoptotic cells were identified using the TUNEL method. Tumour specimen of 67 resected patients was included in the study. By univariate analysis, survival was influenced by Survivin overexpression. The nuclear Survivin overexpression was associated with better prognosis (P ¼ 0.0009), while its cytoplasmic overexpression resulted a negative prognostic factor (P ¼ 0.0127). Also, the apoptotic index was a statistically significant prognostic factor in a univariate model (P ¼ 0.0142). By a multivariate Cox regression analysis, both the nuclear (P ¼ 0.002) and cytoplasmic (P ¼ 0.040) Survivin overexpression maintained the prognostic statistical value. This is the first study reporting a statistical significant prognostic relevance of nuclear and cytoplasmic Survivin overexpression in pancreatic cancer. In particular, patients with high nuclear Survivin staining showed a longer survival, whereas patients with high cytoplasmic Survivin staining had a shorter overall survival.

show abstract

mentioning

confidence: 99%

Nuclear and cytoplasmic expression of survivin in 67 surgically resected pancreatic cancer patients

et al. 2005

View full text Add to dashboard Cite

show abstract

“…[12][13][14][15] Survivin is highly expressed in fetal tissues but is not found in most normal adult tissues. 12 Therefore, the Sur-P should be an excellent candidate for controlling specific expression of therapeutic genes in human tumor cells.…”

Section: Discussionmentioning

confidence: 99%

“…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. For example, downregulation of survivin expression or function induces apoptotic cell death specifically in tumor cells and enhances the antitumor effects of several chemotherapy drugs.…”

Section: Introductionmentioning

confidence: 98%

“…11 It is expressed in 60-70% of many common tumor types but not in normal, differentiated adult tissues. [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.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Yang

Cao

et al. 2004

Gene Ther

View full text Add to dashboard Cite

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.

show abstract

“…One family of genes regulated by NFkB are IAPs, acting as suppressors of apoptosis by inhibiting caspase-3, -7 and -9. 9,19 It was suggested that cancer cells, for example, of pancreatic carcinoma, 20,21 can counteract apoptotic signals by the expression of IAPs. We found a pattern of fibrosis-associated enhancement of cIAP1 and survivin protein expression similar to RelA emerge in islets.…”

Section: Discussionmentioning

confidence: 99%

Parenchymal regression in chronic pancreatitis spares islets reprogrammed for the expression of NFκB and IAPs

Hasel

Bhanot

Heydrich

et al. 2005

Laboratory Investigation

View full text Add to dashboard Cite

In advanced chronic pancreatitis (CP), islets are preserved even in the midst of scarring. We recently showed in CP local production of interferon (IFN)c, transforming growth factor (TGF)b and death receptor ligand TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), along with functional death receptor neoexpression and apoptosis in exocrine but not in endocrine cells. However, islets are strongly induced for TRAILreceptor(R)-4 lacking the functional death domain. TRAIL-R4 signaling in T cells induces NFjB, which activates antiapoptotic programs. Here, we demonstrate that in insulinoma cells CM, TGFb/IFNc/TRAIL in combination induced TRAIL-R4 surface expression. TRAIL/IFNc upregulated NFjB subunits and its target gene survivin while downmodulating IjBa mRNA. RelA transcriptional activity increased upon stimulation with IFNc and IFNc/ TRAIL. In situ, normal pancreatic epithelia had low mRNA levels of NFjB subunits. These were higher in parenchymal areas of CP with severe fibrosis and highest in islets. NFjB-regulated proteins IjBa, survivin and another apoptosis inhibitor, cIAP1, were found in corresponding sites, again at highest levels in islets surrounded by fibrosis. In conclusion, islets in CP not only evade immune attack by nonexposure of functional death receptors in the presence of TRAIL-R4 but also additionally neoexpress NFjB and its target genes, survivin and cIAP1, to protect themselves from apoptosis.

show abstract

Expression of survivin is correlated with cancer cell apoptosis and is involved in the development of human pancreatic duct cell tumors

Cited by 247 publications

References 12 publications

Nuclear and cytoplasmic expression of survivin in 67 surgically resected pancreatic cancer patients

Nuclear and cytoplasmic expression of survivin in 67 surgically resected pancreatic cancer patients

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

Parenchymal regression in chronic pancreatitis spares islets reprogrammed for the expression of NFκB and IAPs

Contact Info

Product

Resources

About