Differentially expressed genes in radioresistant nasopharyngeal cancer cells: gp96 and GDF15

Chang, Joseph Tung-Chieh; Chan, Shih-Hsuan; Lin, Chien‐Yu; Lin, Tzu‐En; Wang, Hung‐Ming; Liao, Chun‐Ta; Wang, Tzu‐Hao; Lee, Li‐Yu; Cheng, Ann‐Joy

doi:10.1158/1535-7163.mct-06-0801

Cited by 78 publications

(72 citation statements)

References 29 publications

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“…Previous studies have screened for DEPs associated with radioresistance in NPC (4,10). One study identified seven upregulated genes in radioresistant subclones of CNE2.…”

Section: Discussionmentioning

confidence: 99%

Protein expression of nucleophosmin, annexin A3 and nm23-H1 correlates with human nasopharyngeal carcinoma radioresistance in vivo

Liang

et al. 2016

Oncology Letters

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Abstract. Radioresistance is a significant obstacle in the treatment of endemic nasopharyngeal carcinoma (NPC). The present study aimed to identify proteins associated with radioresistance in NPC in vitro and in vivo. Proteomics analyses were conducted to screen for differentially-expressed proteins (DEPs) in parental CNE-2 cells and CNE-2R cells. Using proteomics approaches, 16 DEPs were identified. Of these DEPs, nucleophosmin (NPM1), annexin A3 and nm23-H1, were verified using western blot analyses. The tumorigenicity was investigated using mouse xenograft tumorigenicity assays, and tumor growth curves were generated. The protein expression of NPM1, annexin A3 and nm23-H1 was examined by immunohistochemically staining tumor tissues. NPM1 and annexin A3 protein levels were downregulated in the CNE-2R cells, whereas nm23-H1 expression was upregulated. In vivo tests showed that compared with the CNE-2 tumors, CNE-2R tumor growth was significantly retarded (P<0.05). CNE-2 tumor progression was inhibited by irradiation, but CNE-2R tumor progression was not, indicating that the CNE-2R cells were also radioresistant in vivo. NPM1 and annexin A3 expression was significantly lower in non-irradiated (NIR)-CNE-2R tumors compared with NIR-CNE-2 tumors (P<0.01). However, Nm23-H1 protein levels were significantly higher (P<0.05). Overall, the present study established comparable radioresistant and radiosensitive tumor models of human NPC, and identified candidate biomarkers that may correlate with radioresistance. The data showed that dysregulation of NPM1, annexin A3 and nm23-H1 expression correlated with the cellular and tumor radioresponse. These proteins are involved in the regulation of intracellular functions, including stress responses, cell proliferation and DNA repair. However, further clinical evaluations are required.

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“…Previous studies have screened for DEPs associated with radioresistance in NPC (4,10). One study identified seven upregulated genes in radioresistant subclones of CNE2.…”

Section: Discussionmentioning

confidence: 99%

Protein expression of nucleophosmin, annexin A3 and nm23-H1 correlates with human nasopharyngeal carcinoma radioresistance in vivo

Liang

et al. 2016

Oncology Letters

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“…11). All the cell culture conditions were the same as previously reports (9)(10)(11). The Matrigel invasion method was used to establish HNC cell sublines with a high invasive capability, similar to what has been previously described (12).…”

Section: Establishment and Characterization Of Highly Invasive Hnc Cementioning

confidence: 99%

“…The pTOPO-U6 vector was used to construct Hsp60-, GANAB-, Gp96-, and Grp78-short hairpin RNA (shRNA) plasmids as previously described (9). Briefly, a 15 to 18 sense and antisense complementary hairpin oligonucleotide was generated against a specific mRNA sequence of each gene, following cloned into pTOPO-U6 vector.…”

Section: Cloning and Transfection Of Short Hairpin Rna Plasmidsmentioning

confidence: 99%

Molecular Chaperones as a Common Set of Proteins That Regulate the Invasion Phenotype of Head and Neck Cancer

Chiu

Lin

Lee

et al. 2011

Clinical Cancer Research

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Purpose: The goal of this study was to establish a common set of molecules that regulate cell invasion in head and neck cancer (HNC).Experimental Design: Five invasive sublines derived from HNC cell lines were established using the Matrigel selection method. Proteomic technology, MetaCore algorithm, and reverse transcriptase-PCR methods were used to search for molecules that contribute to the invasion phenotype. Cellular functional analyses and clinical association studies were applied to examine the significance of the molecules.Results: Fifty-two proteins were identified in more than two of the four independent proteomic experiments, including 10 (19%) molecular chaperones. Seven chaperones were confirmed to be differentially expressed in five sublines, Hsp90a, Hsp90b, Hsp90-B1/Gp96, Hsp70-A5/Grp78, and HYOU1, that upregulate, whereas Hsp60 and glucosidase-a neutral AB (GANAB) downregulate. Four molecules were further investigated. In all cell lines, knockdown of Hsp60 or GANAB and silencing of Gp96 or Grp78 considerably enhanced or reduced cell migration and invasion, respectively. Clinical association studies consistently revealed that low levels of Hsp60 or GANAB and high levels of Gp96 or Grp78 are significantly associated with advanced cancer (P < 0.001 to P ¼ 0.047, respectively, for the four molecules) and poor survival (P < 0.001 to P ¼ 0.025, respectively, for the four molecules).Conclusion: Our study defined molecular chaperones as a common set of proteins that regulate the invasion phenotype of HNC. Loss of the tumor suppression function of Hsp60 or GANAB and acquisition of the oncogenic function of Gp96 or Grp78 contribute to aggressive cancers. These molecules may serve as prognostic markers and targets for cancer drug development.

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“…Microarrays have been used to assess genes involved in radioresistance in various types of cancer (6)(7)(8)(9)(10)(11). For examples, analysis for gene expression profiles of radioresistant NPC cell lines using a cDNA array found that at least two genes, gp96 and GDF15, involved in the radioresistance of NPC cell lines (11).…”

Section: Introductionmentioning

confidence: 99%

Identification of Biomarkers for Predicting Nasopharyngeal Carcinoma Response to Radiotherapy by Proteomics

et al. 2010

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Radiotherapy is the primary treatment for nasopharyngeal cancer (NPC), but radioresistance remains a serious obstacle to successful treatment in many cases. To identify the proteins involved in this resistance and to evaluate their potential for predicting NPC response to radiotherapy, we first established a radioresistant subclone cell line (CNE2-IR) derived from NPC cell line CNE2 by treating the cells with five rounds of sublethal ionizing radiation. Proteomics was then performed to compare the protein profiles of CNE2-IR and CNE2, and a total of 34 differential proteins were identified. Among them, 14-3-3σ and Maspin were downregulated and GRP78 and Mn-SOD were upregulated in the radioresistant CNE2-IR compared with control CNE2, which was conformed by Western blot. Immunohistochemistry was performed to detect the expression of the four validated proteins in the 39 radioresistant and 51 radiosensitive NPC tissues and their value for predicting NPC response to radiotherapy were evaluated by receiver operating characteristic analysis. The results showed that the downregulation of 14-3-3σ and Maspin and the upregulation of GRP78 and Mn-SOD were significantly correlated with NPC radioresistance and the combination of the four proteins achieved a sensitivity of 90% and a specificity of 88% in discriminating radiosensitive from radiaoresistant NPC. Furthermore, the resistance to ionizing radiation can be partially reversed by the overexpression of 14-3-3σ in the CNE2-IR. The data suggest that 14-3-3σ, Maspin, GRP78, and Mn-SOD are potential biomarkers for predicting NPC response to radiotherapy and their dysregulation may be involved in the radioresistance of NPC. Cancer Res; 70(9); 3450-62. ©2010 AACR.

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Differentially expressed genes in radioresistant nasopharyngeal cancer cells: gp96 and GDF15

Abstract: Radiotherapy is the major treatment modality for nasopharyngeal cancer

Cited by 78 publications

References 29 publications

Protein expression of nucleophosmin, annexin A3 and nm23-H1 correlates with human nasopharyngeal carcinoma radioresistance in vivo

Protein expression of nucleophosmin, annexin A3 and nm23-H1 correlates with human nasopharyngeal carcinoma radioresistance in vivo

Molecular Chaperones as a Common Set of Proteins That Regulate the Invasion Phenotype of Head and Neck Cancer

Identification of Biomarkers for Predicting Nasopharyngeal Carcinoma Response to Radiotherapy by Proteomics

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