Glutathione S-Transferase π Expression in Nasopharyngeal Cancer

Jayasurya, Anita; Yap, Wai-Ming; Tan, Nam-Guan; Tan, B. T. G.; Bay, Boon‐Huat

doi:10.1001/archotol.128.12.1396

Cited by 7 publications

(3 citation statements)

References 23 publications

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“…GSTP1 is a significant downstream molecule in the EGFR signaling network, and EGFR-regulated phosphorylated GSTP1 is responsible for chemo resistance in NPC cells [44,46]. Further studies found that GSTP1 was also associated with lymphogenous metastasis in NPC [47], and this may lead to poor prognosis. Next, we focus on radiation-resistant NPC cells.…”

Section: Discussionmentioning

confidence: 99%

Epidermal growth factor receptor could play a prognostic role to predict the outcome of nasopharyngeal carcinoma: A meta-analysis

Huang

et al. 2014

CBM

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Section: Discussionmentioning

confidence: 99%

Epidermal growth factor receptor could play a prognostic role to predict the outcome of nasopharyngeal carcinoma: A meta-analysis

Huang

et al. 2014

CBM

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“…Chen reported that 58% (83/143) primary NPC, 69.8% (30/43) recurrent NPC, and 65% (13/20) metastatic NPC tissues highly expressed GSTP1 [29]. Jayasurya reported that all 55 NPC tissues showed positive GSTP1 immunoreactivity, and a significant correlation was found between GSTP1 expression and regional nodal metastasis of NPC [30]. In tumors with EGFR aberrant activation, GSTP1 was phosphorylated and activated, leading to drug inactivation and drug resistance [31].…”

Section: Discussionmentioning

confidence: 99%

Analysis of EGFR signaling pathway in nasopharyngeal carcinoma cells by quantitative phosphoproteomics

Ruan

Wan

et al. 2011

Proteome Sci

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BackgroundThe epidermal growth factor receptor (EGFR) is usually overexpressed in nasopharyngeal carcinoma (NPC) and is associated with pathogenesis of NPC. However, the downstream signaling proteins of EGFR in NPC have not yet been completely understood at the system level. The aim of this study was identify novel downstream proteins of EGFR signaling pathway in NPC cells.ResultsWe analyzed EGFR-regulated phosphoproteome in NPC CNE2 cells using 2D-DIGE and mass spectrometry analysis after phosphoprotein enrichment. As a result, 33 nonredundant phosphoproteins including five known EGFR-regulated proteins and twenty-eight novel EGFR-regulated proteins in CNE2 were identified, three differential phosphoproteins were selectively validated, and two differential phosphoproteins (GSTP1 and GRB2) were showed interacted with phospho-EGFR. Bioinformatics analysis showed that 32 of 33 identified proteins contain phosphorylation modification sites, and 17 identified proteins are signaling proteins. GSTP1, one of the EGFR-regulated proteins, associated with chemoresistance was analyzed. The results showed that GSTP1 could contribute to paclitaxel resistance in EGF-stimulated CNE2 cells. Furthermore, an EGFR signaling network based on the identified EGFR-regulated phosphoproteins were constructed using Pathway Studio 5.0 software, which includes canonical and novel EGFR-regulated proteins and implicates the possible biological roles for those proteins.ConclusionThe data not only can extend our knowledge of canonical EGFR signaling, but also will be useful to understand the molecular mechanisms of EGFR in NPC pathogenesis and search therapeutic targets for NPC.

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“…One plausible explanation for this observed phenomenon is that the Bcl-2 protein has been implicated as a regulator of transport through the nuclear pore (21). GST-pi, which has a molecular weight of 22 kDa, has the potential to gain entry into the nucleus through the nuclear pore complex (22). The precise role of GST-pi in the nucleus has not been ascertained, although an increased amount of nuclear GST-pi expression has been observed in breast cancer cells resistant to doxorubicin and cis-diamminedichloroplatinum (II; 23).…”

Section: Figurementioning

confidence: 99%

Prognostic Significance of Glutathione S-Transferase-Pi in Invasive Breast Cancer

et al. 2003

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Glutathione S-transferase pi (GST-pi), a Phase II detoxification enzyme, has recently been implicated in protection against apoptosis. Expression of GST-pi and Bcl-2 protein, an established apoptosis marker, was analyzed by immunohistochemistry in 116 cases of infiltrative ductal breast carcinomas in Singapore women. The markers were correlated with apoptosis detected by the TUNEL method and clinico-pathological parameters. There were 67 (58%) GST-pi-positive breast tumors and 43 (37%) Bcl-2-positive tumors. In a large proportion of GSTpi-positive/Bcl-2-positive tumors, there was a distinct accumulation of the GST-pi enzyme within the nucleus of cancer cells when examined by double immunofluorescence labeling under confocal microscopy. GST-pi immunoreactivity was not significantly correlated with any of the traditional histologic factors known to influence prognosis, whereas Bcl-2 overexpression was associated with reduced size of primary tumor (P ‫؍‬ .021) and positive estrogen receptor status (P ‫؍‬ .001). Univariate analysis revealed that GST-pi-positive, Bcl-2-positive, and lower histological grade tumors had decreased levels of apoptosis (P ‫؍‬ .024, P ‫؍‬ .011, and P ‫؍‬ .029, respectively). However, multivariate analysis showed that histological grade and Bcl-2, but not GST-pi, immunoreactivity were correlated with apoptotic status. The Kaplan-Meier disease-free survival curves showed a significant difference between GST-pi-positive and GST-pi-negative breast cancer cases (P ‫؍‬ .002). Disease-free survival in patients with GST-pi-positive tumors was also worse than that in patients with GST-pi-negative tumors in the group who had adjuvant chemotherapy (P ‫؍‬ .04). In patients who were lymph node positive, GST-pi immunopositivity was found to influence disease-free survival. Recurrence of tumors was also significantly affected by GST-pi immunoreactivity (relative risk of 8.1). The findings indicate that GST-pipositive tumors are more aggressive and have a poorer prognosis than do corresponding GST-pinegative breast cancers.

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Glutathione S-Transferase π Expression in Nasopharyngeal Cancer

Abstract: Nasopharyngeal tumor cells may respond to pro-oxidant conditions by modulating intracellular antioxidant defense. Glutathione S-transferase pi expression appears to be associated with lymphogenous metastasis in NPC.

Cited by 7 publications

References 23 publications

Epidermal growth factor receptor could play a prognostic role to predict the outcome of nasopharyngeal carcinoma: A meta-analysis

Epidermal growth factor receptor could play a prognostic role to predict the outcome of nasopharyngeal carcinoma: A meta-analysis

Analysis of EGFR signaling pathway in nasopharyngeal carcinoma cells by quantitative phosphoproteomics

Prognostic Significance of Glutathione S-Transferase-Pi in Invasive Breast Cancer

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