Overexpression and significance of prion protein in gastric cancer and multidrug‐resistant gastric carcinoma cell line SGC7901/ADR

Du, Jing-ping; Pan, Yanglin; Shi, Yongquan; Guo, Changcun; Jin, Xiaohang; Lee, Sun; Liu, Na; Qiao, Tiankui; Fan, Daiming

doi:10.1002/ijc.20570

Cited by 94 publications

(107 citation statements)

References 29 publications

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“…For example, tumor resistance to TNFa has been associated with increased PrP C expression. 17 PrP C levels have also been found to be up-regulated in adriamycin-resistant gastric carcinoma, 18 with suppression of PrP C partially reversing this phenotype in gastric and breast carcinoma cells. 18 PrP C overexpression in gastric tumor cell lines has also been associated with increased expression of Bcl-2, and decreased expression of p53 and Bax, indicating a possible increase in resistance to programmed cell death.…”

Section: Uiccmentioning

confidence: 99%

“…17 PrP C levels have also been found to be up-regulated in adriamycin-resistant gastric carcinoma, 18 with suppression of PrP C partially reversing this phenotype in gastric and breast carcinoma cells. 18 PrP C overexpression in gastric tumor cell lines has also been associated with increased expression of Bcl-2, and decreased expression of p53 and Bax, indicating a possible increase in resistance to programmed cell death. [18][19][20] In the absence of PrP C expression, resistance to TRAIL-induced apoptosis was inhibited in breast adriamycinresistant carcinoma cells.…”

Section: Uiccmentioning

confidence: 99%

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Prion protein ablation increases cellular aggregation and embolization contributing to mechanisms of metastasis

Muras¹,

Hajj²,

Ribeiro

et al. 2009

Intl Journal of Cancer

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Section: Uiccmentioning

confidence: 99%

Section: Uiccmentioning

confidence: 99%

Prion protein ablation increases cellular aggregation and embolization contributing to mechanisms of metastasis

Muras¹,

Hajj²,

Ribeiro

et al. 2009

Intl Journal of Cancer

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“…Conversely, we recently established that PrP c overexpression led to an increased staurosporine-evoked cell death (13) in transfected or inducible cell lines and showed that this cellular response was associated with an activation of caspase-3 linked to a transcriptional and post-transcriptional control of the p53 transcription factor (14). Moreover, we and others have described that down-regulation of PrP c in cell lines (14,15) or deletion in vivo decreased p53 expression (14,16). This last observation would plead for a p53-dependent proapoptotic function of PrP c rather than a protective one given the pivotal role of this tumor suppressor in triggering cell death.…”

mentioning

confidence: 93%

The C-terminal Products of Cellular Prion Protein Processing, C1 and C2, Exert Distinct Influence on p53-dependent Staurosporine-induced Caspase-3 Activation

Sunyach¹,

Cissé

Costa

et al. 2007

Journal of Biological Chemistry

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The cellular prion protein (PrP c ) undergoes various endoproteolytic attacks within its N-terminal domain, leading to the production of C-terminal fragments (C) tethered to the plasma membrane and soluble N-terminal peptides (N). One of these cleavages occurs at position 110/111, thereby generating C1 and N1 products. We have reported that disintegrins ADAM-10, -9, and -17 participate either directly or indirectly to this proteolytic event. An alternative proteolytic event taking place around residue 90 yields C2 and N2 fragments. The putative function of these proteolytic fragments remained to be established. We have set up two novel human embryonic kidney 293 cell lines stably overexpressing either C1 or C2. We show that C1 potentiates staurosporine-induced caspase-3 activation through a p53-dependent mechanism. Thus, C1 positively controls p53 transcription and mRNA levels and increases p53-like immunoreactivity and activity. C1-induced caspase-3 activation remained unaffected by the blockade of endocytosis in HEK 293 cells and was abolished in p53-deficient fibroblasts. Conversely, overexpression of the C2 fragment did not significantly sensitize HEK 293 cells to apoptotic stimuli and did not modify p53 mRNA levels or activity. Therefore, the nature of the proteolytic cleavage taking place on PrP c yielded C-terminal catabolites with distinct function and could be seen as a switch mechanism controlling the function of the PrP c in cell survival.

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“…Previous studies notified that the mutation of Mdr-1 gene could upregulate the p-glycoprotein expression and PKC-mediated phosphorylation and other associated proteins could directly modify the p-glycoprotein function. [25][26][27][28] Studies are underway to investigate whether Bicyclol affects those correlated mechanisms for reducing p-glycoprotein expression and mediated MDR in both Vin R KB and Adr R MCF-7 cells.…”

Section: Discussionmentioning

confidence: 99%

Chemosensitizing multiple drug resistance of human carcinoma by bicyclol involves attenuated P-glycoprotein, GST-P and Bcl-2

Zhu

Liu²,

Zhao³

et al. 2006

Cancer Biology & Therapy

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Bicyclol, a second generation of synthetic hepatoprotectant being used in China for anti-hepatitis therapy, shows chemosensitizing effect on reverting multiple drug resistance (MDR) of cytostatic agents in two established MDR carcinoma cell lines, vincristine resistant human stomatic epidermoid carcinoma Vin R KB and adriamycin resistant human breast carcinoma Adr R MCF-7. The reversal rate of drug resistance was calculated from the changes of the IC 50 of cell growth inhibition. Bicyclol at the concentration of 25, 50, 100 µM induced 2.8 7.3 and 20.7 fold, respectively, reversal of vincristine resistance in Vin R KB cell. Bicyclol also reversed the cross-resistance of Vin R KB cell to taxol and Adr R MCF-7 cell resistance to adriamycin at the similar range of potency. Further, Bicyclol recovered the reduced accumulation of adriamycin in Adr R MCF-7 cell partially to the level in drugsensitive MCF-7 cell, indicate the inhibition of MDR related membrane efflux pump system. Overexpression of membrane p-glycoprotein coded by Mdr-1 genes, the most common efflux pump correlated to MDR, was found in both Vin R KB and Adr R MCF-7 cells by Western blot and immunocytochemistry as compared with drug-sensitive cells. The p-glycoprotein was decreased to the levels in drug-sensitive cells when Vin R KB and Adr R MCF-7 cells were treated with Bicyclol for 12-72 hours. Both Vin R KB and Adr R MCF-7 cells showed increased GSH contents, and Adr R MCF-7 cell showed increased GST activity and the overexpression of Bcl-2 protein, by which molecules are tightly related to the MDR formation besides Mdr-1 p-glycoprotein. Bicyclol reduced the GSH contents, GST activities and Bcl-2 expression. All these data demonstrate that, by modifying the expressions of Mdr-1, GSH/GST and Bcl-2, Bicyclol increases the intracellular drug concentration and sensitizes the resistant cells to the anti-carcinoma agents.

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Overexpression and significance of prion protein in gastric cancer and multidrug‐resistant gastric carcinoma cell line SGC7901/ADR

Cited by 94 publications

References 29 publications

Prion protein ablation increases cellular aggregation and embolization contributing to mechanisms of metastasis

Prion protein ablation increases cellular aggregation and embolization contributing to mechanisms of metastasis

The C-terminal Products of Cellular Prion Protein Processing, C1 and C2, Exert Distinct Influence on p53-dependent Staurosporine-induced Caspase-3 Activation

Chemosensitizing multiple drug resistance of human carcinoma by bicyclol involves attenuated P-glycoprotein, GST-P and Bcl-2

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