Significance of c-Myc and Bcl-2 Protein Expression in Nasopharyngeal Carcinoma

Yu, Yongqiang; Dong, Weidong; Li, Xin; Yu, Enju; Zhou, Xiaorong; Li, Shuhua

doi:10.1001/archotol.129.12.1322

Cited by 33 publications

(28 citation statements)

References 27 publications

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“…Our results concerning BCL2 gene expression are in accordance with two other independent studies, conducted on Turkish and Chinese patients, which revealed the overexpression of BCL2 in 74.3% and 57.0% of patients, respectively. However, no correlation between BCL2 expression and clinical features was shown in these studies [46,47].…”

Section: Discussionmentioning

confidence: 69%

Quantitative analysis of BCL2 mRNA expression in nasopharyngeal carcinoma: an unfavorable and independent prognostic factor

et al. 2010

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Programmed cell death plays a vital role in a wide variety of physiological processes. Defects in apoptotic cell death contribute to neoplastic diseases by preventing or delaying normal cell death. BCL2 (Bcl-2) is an anti-apoptotic gene with marked up-regulation in various malignancies, such as breast cancer, in which expression of the BCL2 protein has been proposed as a prognostic tumor biomarker. The purpose of the current study was to investigate mRNA expression of the BCL2 gene in nasopharyngeal carcinoma (NPC) biopsies and assess its prognostic value. For this purpose, total RNA was isolated from 89 malignant and hyperplastic nasopharyngeal biopsies from Tunisian patients. After testing the quality of the extracted RNA, cDNA was prepared by reverse transcription. A highly sensitive real-time PCR methodology for BCL2 mRNA quantification was developed using SYBR® Green chemistry. GAPDH served as an endogenous control gene. Relative quantification analysis was performed using the comparative C (T) (2(-∆∆CT)) method. High BCL2 mRNA levels were detected in advanced-stage nasopharyngeal tumors (p = 0.030). Furthermore, BCL2 mRNA expression was strongly associated with lymph node involvement (p = 0.009) and presence of distal metastases (p = 0.013). Survival analysis demonstrated that patients with BCL2-positive nasopharyngeal tumors have significantly shorter disease-free and overall survival (p = 0.011 and p = 0.028, respectively). The major contribution of the current study is the quantification and evaluation, for the first time, of the prognostic significance of the BCL2 mRNA expression in nasopharyngeal carcinoma (NPC) patients. Our results suggest that mRNA expression levels of BCL2 may represent a novel unfavorable and independent tumor biomarker for nasopharyngeal carcinoma.

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Section: Discussionmentioning

confidence: 69%

Quantitative analysis of BCL2 mRNA expression in nasopharyngeal carcinoma: an unfavorable and independent prognostic factor

et al. 2010

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“…However, Bcl-2 is overexpressed in the majority of NPC tumors (61-89%), even in the absence of detectable LMP1 expression, and it is postulated that Bcl-2 may play a critical role in promoting cell survival and mediating resistance to chemotherapeutic agents in NPC. [6][7][8][9][10][11][12] Thus, Bcl-2 represents a rational therapeutic target in NPC.…”

Section: Discussionmentioning

confidence: 99%

“…5 Although a direct link between LMP-1 expression, Bcl-2 upregulation and cell survival in NPC is unclear, the majority of NPC tumors overexpress Bcl-2, even in the absence of LMP-1 expression. [6][7][8][9][10][11][12] Given the antiapoptotic function of Bcl-2 and its role in conferring resistance to chemotherapy, it represents a rational target for modulation using antisense strategies in NPC.…”

Section: Epstein-barr Virus (Ebv) Is Causally Linked To Undifferentiamentioning

confidence: 99%

“…Animals were injected with 5 million C666-1 and randomized to CDDP (diamonds), CDDP 1 2 base mismatch control oligo MM (triangles) or CDDP 1 G3139 (squares) (n 5 5-6 per arm). Treatment with oligo was initiated on day 7 at a dose of 25 mg/kg every 3 days 3 5 doses (days [7][8][9][10][11][12][13][14][15][16][17][18][19][20]. CDDP was administered on day 14 (8 mg/kg 3 1).…”

Section: G3139 Inhibits C666-1 Growth and Enhances Sensitivity To Cddmentioning

confidence: 99%

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Systemic Bcl‐2 antisense oligodeoxynucleotide in combination with cisplatin cures EBV⁺ nasopharyngeal carcinoma xenografts in SCID mice

Lacy

Loomis

Grill

et al. 2006

Intl Journal of Cancer

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Nasopharyngeal carcinoma (NPC) is causally linked to Epstein‐Barr virus (EBV), and the EBV oncoprotein, latent membrane protein 1 (LMP‐1), is expressed in the majority of NPCs. LMP‐1 upregulates antiapoptotic genes, including bcl‐2, and Bcl‐2 protein is overexpressed in NPC. Given the antiapoptotic and chemoprotective effects of Bcl‐2, it represents a rational therapeutic target in NPC. We have investigated the antitumor and chemosensitizing effects of the Bcl‐2 antisense oligodeoxynucleotide G3139 (oblimersen, Genasense) in NPC. For these studies, we used the C666‐1 line, a stably infected NPC‐derived line that co‐expresses LMP‐1 and Bcl‐2. We have shown that G3139 treatment of C666‐1 in vitro caused sequence‐dependent suppression of Bcl‐2 protein, inhibition of cell growth and enhanced sensitivity to cisplatin (CDDP), as measured by increased antiproliferative and apoptotic effects. In vivo, G3139 treatment (25 mg/kg every 3 days × 5 doses) delayed engraftment and significantly inhibited growth of established C666‐1 xenografts in SCID mice compared to control oligo‐treated animals. However, G3139 alone did not prevent engraftment or cure established tumors in any animals. In contrast, G3139 treatment (25 mg/kg every 3 days × 5 starting on day 7) in combination with CDDP (8 mg/kg on day 14) completely abrogated tumor engraftment in 80% of animals compared to CDDP (0%) or CDDP + control oligo (0%). When treatment was delayed until tumor was established, G3139 in combination with CDDP significantly inhibited tumor growth compared to CDDP or CDDP + control oligo, and cured 69% animals with established tumors. No animals treated with G3139, CDDP or CDDP + control oligo were cured. Tumor burden and response to treatment correlated with EBV DNA load in serum, measured by real‐time PCR. Western blots of tumor extracts obtained during oligo treatment showed that Bcl‐2 levels were significantly decreased in G3139‐treated animals. Our studies have demonstrated that the Bcl‐2 antisense oligodeoxynucleotide, G3139, has proapoptotic effects in C666‐1, and in combination with CDDP, is curative in C666‐1 NPC xenograft tumors in vivo. The sequence‐dependency of these effects is consistent with an antisense mechanism. These studies suggest that Bcl‐2 may represent a biologically relevant target for the development of novel combinatorial therapies for NPC. © 2006 Wiley‐Liss, Inc.

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“…More and more scholars have accepted the theory that tumors originate from CSCs. In addition to the above characteristics, CSCs also express several relatively specific biomarkers, such as CD133 [5], CD44 [6], NaNOG [7], and SOX2 [8], and overexpress anti-apoptotic genes, oncogenes, and other malignant biological markers, including telomerase and its hTERT subunit [9], BcL-2 [10], and survivin [11]. CSCs, tumor-like stem cells, or side population cells have been isolated from a variety of malignant tumors, including NPC [12,13].…”

Section: Introductionmentioning

confidence: 99%

The Pinx1 Gene Downregulates Telomerase and Inhibits Proliferation of CD133+ Cancer Stem Cells Isolated from a Nasopharyngeal Carcinoma Cell Line by Regulating Trfs and Mad1/C-Myc/p53 Pathways

Shen

Chen

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Cancer stem cells (CSCs) are important factors for the continuous growth, recurrence, and metastasis of malignant tumors. They are responsible for the ineffectiveness of traditional radiotherapy and chemotherapy toward malignant tumors. Currently, stem cells or side-population cells have been isolated from many cancer cell lines and malignant tumor tissues, including nasopharyngeal carcinoma. Exploring the biological characteristics of CSCs for CSC-targeted therapy has gained importance. CSCs possess higher telomerase activity; thus, the use of the gene encoding telomerase inhibitor PinX1 gene to target telomerase in CSCs and inhibit proliferation, invasion, and metastasis of CSCs has become an important means for the treatment of malignant tumors. PinX1 may regulate complex pathways, including TRF1, Mad1/c-Myc, and p53. Methods: In this study, nasopharyngeal CD133+ CSCs were sorted using CD133 immunomagnetic beads by flow cytometry The successful isolation of CD133+ CSCs was confirmed by examining their surface markers, namely CD44, NaNOG, and SOX2 as well as their ability to undergo in vivo tumorigenesis and in vitro sphere formation, proliferation, migration, and invasion. In addition, CD133+ CSCs were transfected with the constructed PinX1 overexpression plasmid or siRNA and the resulting effects on their proliferation, migration, invasion, and apoptosis were detected using cell counting kit-8 (CCK-8), transwell assay, and scratch test, respectively. Furthermore, their effects on mRNA and protein levels of TRF1, TRF2, Mad1, c-Myc, and p53 were examined using quantitative real-time PCR and western blot, respectively. Results: The overexpression of PinX1 in CD133⁺ CSCs significantly decreased hTERT (P < 0.001), inhibited proliferation, migration, and invasion, induced apoptosis, and significantly decreased c-Myc mRNA levels (P < 0.001), while it increased TRF1, Mad1, and p53 mRNA levels (all P < 0.001). On the other hand, PinX1 silencing in CD133⁺ CSCs significantly decreased TRF1, Mad1, and p53 mRNA levels (all P < 0.01), while it increased hTERT and c-Myc mRNA levels (all P < 0.05). Conclusion: These results indicate that PinX1 downregulates telomerase activity in CD133⁺ CSCs, inhibits its proliferation, migration, and invasion, and induces apoptosis possibly through TRF1, Mad1/c-Myc, and p53–mediated pathways.

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Significance of c-Myc and Bcl-2 Protein Expression in Nasopharyngeal Carcinoma

Abstract: Expression of Bcl-2 and c-Myc protein seems to be a useful marker to reflect irradiation response and to predict illness condition and patient outcome.

Cited by 33 publications

References 27 publications

Quantitative analysis of BCL2 mRNA expression in nasopharyngeal carcinoma: an unfavorable and independent prognostic factor

Quantitative analysis of BCL2 mRNA expression in nasopharyngeal carcinoma: an unfavorable and independent prognostic factor

Systemic Bcl‐2 antisense oligodeoxynucleotide in combination with cisplatin cures EBV⁺ nasopharyngeal carcinoma xenografts in SCID mice

The Pinx1 Gene Downregulates Telomerase and Inhibits Proliferation of CD133+ Cancer Stem Cells Isolated from a Nasopharyngeal Carcinoma Cell Line by Regulating Trfs and Mad1/C-Myc/p53 Pathways

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Significance of c-Myc and Bcl-2 Protein Expression in Nasopharyngeal Carcinoma

Abstract: Expression of Bcl-2 and c-Myc protein seems to be a useful marker to reflect irradiation response and to predict illness condition and patient outcome.

Cited by 33 publications

References 27 publications

Quantitative analysis of BCL2 mRNA expression in nasopharyngeal carcinoma: an unfavorable and independent prognostic factor

Quantitative analysis of BCL2 mRNA expression in nasopharyngeal carcinoma: an unfavorable and independent prognostic factor

Systemic Bcl‐2 antisense oligodeoxynucleotide in combination with cisplatin cures EBV+ nasopharyngeal carcinoma xenografts in SCID mice

The Pinx1 Gene Downregulates Telomerase and Inhibits Proliferation of CD133+ Cancer Stem Cells Isolated from a Nasopharyngeal Carcinoma Cell Line by Regulating Trfs and Mad1/C-Myc/p53 Pathways

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Systemic Bcl‐2 antisense oligodeoxynucleotide in combination with cisplatin cures EBV⁺ nasopharyngeal carcinoma xenografts in SCID mice