Authentication of nasopharyngeal carcinoma tumor lines

Chan, Samantha; Choy, Kwong Wai; Tsao, Sai Wah; Tao, Qian; Tang, Tao; Chung, Grace; Lo, Kwok Wai

doi:10.1002/ijc.23374

Cited by 99 publications

(103 citation statements)

References 12 publications

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“…Similar to our results here, loss of p53 expression was recently shown to inhibit HDACi-induced lytic reactivation (12), while overexpression of p53 was reported to enhance early EBV lytic infection (54). Our finding that endogenous p53 expression appears to cooperate with Na to induce lytic EBV expression in CNE2-Akata and Hone-Akata cells, but not in C666-1 cells, is possibly explained by the fact that C666-1 cells contain only a mutant form of p53 (64), whereas the CNE2-Akata and Hone-Akata lines, although originally described as NPC lines, are at least partially derived from HeLa cells (11) and thus may express some wild-type p53 as well as mutant p53. Alternatively, the p53 mutant found in CNE2-Akata and Hone-Akata cells (p53 Thr280) retains the ability to cooperate with Na to disrupt viral latency.…”

Section: Downloaded Frommentioning

confidence: 83%

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The Epstein-Barr Virus BRRF1 Protein, Na, Induces Lytic Infection in a TRAF2- and p53-Dependent Manner

Hagemeier

Barlow

Kleman

et al. 2011

J Virol

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The Epstein-Barr virus (EBV) BRRF1 lytic gene product (Na) is encoded within the same immediate-early region as the BZLF1 (Z) and BRLF1(R) gene products, but its role during EBV infection has not been well defined. We previously showed that Na cooperates with the R protein to induce lytic gene expression in latently infected EBV-positive 293 cells, and in some EBV-negative cell lines it can activate the Z promoter in reporter gene assays. Here we show that overexpression of Na alone is sufficient to induce lytic gene expression in several different latently infected epithelial cell lines (Hone-Akata, CNE2-Akata, and AGS-Akata), while knockdown of endogenous Na expression reduces lytic gene expression. Consistent with its ability to interact with tumor necrosis factor receptor-associated factor 2 (TRAF2) in a yeast two-hybrid assay, we demonstrate that Na interacts with TRAF2 in cells. Furthermore, we show that TRAF2 is required for Na induction of lytic gene expression, that Na induces Jun N-terminal protein kinase (JNK) activation in a TRAF2-dependent manner, and that a JNK inhibitor abolishes the ability of Na to disrupt viral latency. Additionally, we show that Na and the tumor suppressor protein p53 cooperate to induce lytic gene expression in epithelial cells (including the C666-1 nasopharyngeal carcinoma cell line), although Na does not appear to affect p53 function. Together these data suggest that Na plays an important role in regulating the switch between latent and lytic infection in epithelial cells and that this effect requires both the TRAF2 and p53 cellular proteins.

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Section: Downloaded Frommentioning

confidence: 83%

“…CNE2-Akata cells contain an arginine-to-threonine mutation at codon 280 of p53 (20) as well as wild-type p53 (11). C666-1 cells, an NPC line, were maintained in RPMI medium supplemented with 10% FBS and penicillinstreptomycin and were grown on plates treated with fibronectin (Sigma).…”

Section: Ebv Cell Linesmentioning

confidence: 99%

The Epstein-Barr Virus BRRF1 Protein, Na, Induces Lytic Infection in a TRAF2- and p53-Dependent Manner

Hagemeier

Barlow

Kleman

et al. 2011

J Virol

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“…In this study, several considerations for utilizing HK1 include its origin from an EBV-negative NPC and p53 status, such that the cell line would be naive to the effects of EBV and mimic intact p53 mechanisms in NPC tumors (19,20,31). Although heterozygous for a mutation in p53 (codon 130), HK1 cells still can activate p53-dependent targets such as PUMA and still are responsive to p53 stabilization and growth arrest induced by Nutlin-3 treatment (20,23,(31)(32)(33) and data not shown). In stably transduced HK1 cells, LMP1 and LMP2A coexpression did not affect cell growth, with a subtle increase in motility to fibronectin (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…HK1 cells are one of the few authenticated NPC cell lines that are sensitive to serum deprivation and chemotherapeutics but can resist these cell death treatments by infection with EBV (6,23,31). Additionally, HK1 cells are free of HeLa contamination, which confounds the interpretation of many NPC-derived cell lines (32,33). To investigate cell death responses activated by DNA damage, HK1 cell lines were treated with several DNA-damaging reagents and replication stress inducers, including the topoisomerase II inhibitor etoposide, ionizing radiation, methyl methanesulfonate (MMS), and aphidicolin.…”

Section: Importancementioning

confidence: 99%

Regulation of DNA Damage Signaling and Cell Death Responses by Epstein-Barr Virus Latent Membrane Protein 1 (LMP1) and LMP2A in Nasopharyngeal Carcinoma Cells

Wasil

Wei

Chang

et al. 2015

J Virol

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Nasopharyngeal carcinoma (NPC) is closely associated with latent Epstein-Barr virus (EBV) infection. Although EBV infection of preneoplastic epithelial cells is not immortalizing, EBVcan modulate oncogenic and cell death mechanisms. The viral latent membrane proteins 1 (LMP1) and LMP2A are consistently expressed in NPC and can cooperate in bitransgenic mice expressed from the keratin-14 promoter to enhance carcinoma development in an epithelial chemical carcinogenesis model. In this study, LMP1 and LMP2A were coexpressed in the EBV-negative NPC cell line HK1 and examined for combined effects in response to genotoxic treatments. In response to DNA damage activation, LMP1 and LMP2A coexpression reduced ␥H2AX (S139) phosphorylation and caspase cleavage induced by a lower dose (5 M) of the topoisomerase II inhibitor etoposide. Regulation of ␥H2AX occurred before the onset of caspase activation without modulation of other DNA damage signaling mediators, including ATM, Chk1, or Chk2, and additionally was suppressed by inducers of DNA single-strand breaks (SSBs) and replication stress. Despite reduced DNA damage repair signaling, LMP1-2A coexpressing cells recovered from cytotoxic doses of etoposide; however, LMP1 expression was sufficient for this effect. LMP1 and LMP2A coexpression did not enhance cell growth, with a moderate increase of cell motility to fibronectin. This study supports that LMP1 and LMP2A jointly regulate DNA repair signaling and cell death activation with no further enhancement in the growth properties of neoplastic cells. E pstein-Barr virus (EBV) is a human gammaherpesvirus that establishes lifelong latency in memory B cells, with sporadic reactivation and transmission from oral epithelia (1). More than 90% of the adult population is latently infected, and a subset can develop EBV-associated malignancies, including nasopharyngeal carcinoma (NPC), gastric cancer, Burkitt lymphoma, Hodgkin lymphoma, and lymphomas in the immunocompromised, including AIDS-associated lymphoma and posttransplant lymphoproliferative disease (2, 3). Epithelial cell infection in vitro frequently results in productive replication, and latently infected oral epithelial cells are rare in persistently infected healthy individuals (4, 5). However, epithelial tumors such as NPC consistently express a type II latency program, which includes latent membrane protein 1 (LMP1), LMP2A, and LMP2B (1, 5). Additionally, monoclonal EBV episomes are detected in NPC, suggesting that NPC tumors are the clonal outgrowth of an initially infected cell likely predisposed to oncogenic transformation from additional genetic and environmental cofactors, such as the loss of p16 and exposure to dietary nitrosamines (2, 3). In contrast to the immortalizing properties of EBV to primary B cells, the contribution of EBV infection to epithelial cell oncogenesis is less understood, as infection alone is insufficient to immortalize or induce oncogenic potential in preneoplastic cell lines from the nasopharynx (5, 6).LMP1 and LMP2A transcripts are ...

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“…Cancer cell lines (HNE-1 and CNE-2) were gifted from Miss Jiongyu Chen (Cancer Hospital Zoledronic acid augments the radiosensitivity of cancer cells through perturbing S-and M-phase cyclins and p21 CIP1 expression CHI DU 1,2 , YUYI WANG 1 , HAIJUN LI 2 , YI HUANG 2 , OU JIANG 2 , YANJIE YOU 3,4 and FENG LUO of Shantou University Medical College, Shantou, China) and cultured as described previously (21). The above two cell lines are identified as mixed cancer types (22,23). ZOL was kindly supplied by Novartis Pharma AG (Basel, Switzerland) and diluted in 0.9% saline at a concentration of 10 mM as stock.…”

Section: Methodsmentioning

confidence: 99%

Zoledronic acid augments the radiosensitivity of cancer cells through perturbing S- and M-phase cyclins and p21CIP1 expression

Wang

et al. 2017

Oncology Letters

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Abstract. Radiotherapy and adjuvant chemotherapy have become the standard treatments for multiple types of cancer. Although cancer cells are usually sensitive to radiotherapy, metastasis and local failure still occur mainly due to developed resistance to radiotherapy. Thus, it is critical to improve therapeutics for cancer treatment. The present study demonstrated that third-generation bisphosphonate zoledronic acid (ZOL), even at a low concentration, augments the radiosensitivity of cancer cells exposed to ionizing radiation (IR) by inducing S-phase arrest and subsequently promoting apoptosis. This function of ZOL was associated with elevated levels of cyclin A and cyclin B in the S and M phases, as well as decreased p21 CIP1 expression. In addition, ZOL also inhibited malignant the invasiveness of cancer cells. Notably, these effects could be enhanced concurrently with IR. The present data indicated that combined treatment with ZOL plus IR may be a novel technique to augment the radiosensitivity of cancer cells. IntroductionRadiotherapy and adjuvant chemotherapy have become the standard treatments for multiple types of cancer, including esophageal and nasopharyngeal carcinoma (1,2). Although radiotherapy is widely used to treat early-stage tumors, patients with advanced-stage tumors often experience failure of treatment mainly due to resistance to radiotherapy, resulting in recurrence and distant metastases (2-6). Therefore, the development of potent and reliable radiosensitizers is necessary for improving overall treatment outcomes in cancer therapy.Zoledronic acid (ZOL) is a compound containing nitrogen and bisphosphonates, which harbors anti-reabsorption effects (7). ZOL is used as therapy for bone metastasis in malignancy and a number of metabolic disorders, including bone pain, bone fractures and hypercalcaemia (8,9). ZOL inhibits farnesyl pyrophosphate synthase, a key enzyme in the isoprenoid biosynthetic pathway, and prevents prenylation of small guanosine triphosphate-binding proteins, including Rho, p21 ras , cell division cycle 42, Rac and Rab, which are essential for different cellular functions such as signal transduction and cell adhesion (7-9). ZOL is considered to possess antitumor activity, particularly in combination with chemotherapeutic anticancer drugs (10-12). This effect of ZOL could be observed on cancer cells derived from a variety of tumors, including breast, prostate and pancreatic cancers, by inducing cell apoptosis and inhibiting cell invasion, adhesion and angiogenesis (10-13). Currently, numerous patients with bone metastases secondary to a broad range of solid tumors are benefiting from the antitumor effects of ZOL (14).Our previous study demonstrated the synergistic cytotoxic effects of ZOL and ionizing radiation (IR) on esophageal squamous cell carcinoma and endothelial cells (15). Accordingly, combined treatment with ZOL plus IR may be an encouraging method to treat cancer with less side effects and complications, compared with the use of these agents alone (15)(16)(17)(18)(19...

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Authentication of nasopharyngeal carcinoma tumor lines

Cited by 99 publications

References 12 publications

The Epstein-Barr Virus BRRF1 Protein, Na, Induces Lytic Infection in a TRAF2- and p53-Dependent Manner

The Epstein-Barr Virus BRRF1 Protein, Na, Induces Lytic Infection in a TRAF2- and p53-Dependent Manner

Regulation of DNA Damage Signaling and Cell Death Responses by Epstein-Barr Virus Latent Membrane Protein 1 (LMP1) and LMP2A in Nasopharyngeal Carcinoma Cells

Zoledronic acid augments the radiosensitivity of cancer cells through perturbing S- and M-phase cyclins and p21CIP1 expression

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