Detection of C‐MYC oncogene translocation and copy number change in the normal‐dysplasia‐carcinoma sequence of the larynx by fluorescence in situ hybridization

Yu, Li; Gong, Li‐ping; Dong, Xiaowei; Liu, Honggang

doi:10.1002/dc.22879

Cited by 9 publications

(6 citation statements)

References 29 publications

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“…Caspase-3 is called the death protease because it is a critical executive protease whose activation leads inevitably to apoptosis [25,26]. The C-Myc transcription factor is found constitutively expressed in many cancers; including lung, stomach, breast and colon cancer and also in cervical carcinoma [27][28][29][30]. C-Myc stimulates the expression of many genes and it promotes cell proliferation and inhibits apoptosis [31] [32].…”

Section: Discussionmentioning

confidence: 99%

Over-expression of MEOX2 promotes apoptosis through inhibiting the PI3K/Akt pathway in laryngeal cancer cells

Tian

Tao

et al. 2018

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The early-stage diagnosis and treatment for the recurrence of larynx carcinoma needs further investigation. Mesenchyme homeobox 2 (MEOX2) was speculated as a novel suppressor gene in larynx carcinoma in our study, the molecular mechanism was studied. Real-time quantitative PCR (RT-qPCR) and Western blot were used to detect mRNA and protein levels of MEOX2 in laryngeal cancer tissues and cells (Hep-2, TU212, AMC-NH-8 and TU686 cells), and also apoptosis and phosphoinositide 3-kinase (PI3K)/protein kinase (Akt) related factors in TU212 cells transfected with MEOX2. Cell counting kit-8 (CCK8) assay and Annexin-Ⅴ/PI staining assay were conducted to determine cell viability and apoptosis rates respectively.46 patients with larynx carcinoma were involved in this study. The expression of MEOX2 was lower in larynx carcinoma tissues than normal tissues, correlated with clinical stages, differentiated degrees, and survival times. The expression of MEOX2 was the lowest among those laryngeal cancer cells, and was chosen to be transfected with MEOX2 in the following study. Over-expression of MEOX2 inhibited cell viability and promoted apoptosis of TU212 cells, via increasing the expression levels of Caspase-3, and decreasing levels of C-Myc, XIAP, PI3K p110α, PI3K p110β, PI3K class III and p-Akt. In summary, the expression levels of MEOX2 were inhibited in larynx carcinoma than normal tissues, correlated with the progression of the cancer. Over-expression of MEOX2 in laryngeal cancer cells inhibited cell viability and promoted apoptosis, via regulating apoptosis and PI3K/Akt pathway related factors. It would provide evidence for MEOX2 to be used as a therapeutical gene in larynx carcinoma.

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Section: Discussionmentioning

confidence: 99%

Over-expression of MEOX2 promotes apoptosis through inhibiting the PI3K/Akt pathway in laryngeal cancer cells

Tian

Tao

et al. 2018

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“…The results of the present study suggested that c-Myc overexpression affects the transactivation ability of c-Myc on the Sirt1 promoter in p53 deficient cells, elevating the expression level of Sirt1. The combination of c-Myc overexpression and p53 loss of function may contribute to the elevated expression level of Sirt1 in tumor cells, as cells with high expression levels of Sirt1, including AML, squamous cell carcinoma and diffuse large B-cell lymphoma, demonstrated c-Myc overexpression (24)(25)(26) and p53 loss of function (27). The regulation of Sirt1 expression level by c-Myc and p53 prompted the present study to consider Sirt1 as a target to mediate the oncogenic function of c-Myc.…”

Section: Discussionmentioning

confidence: 99%

p53 inhibits the upregulation of sirtuin 1 expression induced by c-Myc

et al. 2017

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Abstract. Sirtuin 1 (Sirt1), a conserved NAD + dependent deacetylase, is a mediator of life span by calorie restriction. However, Sirt1 may paradoxically increase the risk of cancer. Accordingly, the expression level of Sirt1 is selectively elevated in numerous types of cancer cell; however, the mechanisms underlying the differential regulation remain largely unknown. The present study demonstrated that oncoprotein c-Myc was a direct regulator of Sirt1, which accounts for the upregulation of Sirt1 expression only in the cells without functional p53. In p53 deficient cells, the overexpression of c-Myc increased Sirt1 mRNA and protein expression levels as well as its promoter activity, whereas the inhibitor of c-Myc, 10058-F4, induced decreased Sirt1 basal mRNA and protein expression levels. Deletion/mutation mapping analyses revealed that c-Myc bound to the conserved E-box[-189 to -183 base pair (bp)] of the Sirt1 promoter. In addition, p53 and c-Myc shared at least response element and the presence of p53 may block the binding of c-Myc to the Sirt1 promoter, thus inhibit the c-Myc mediated upregulation of Sirt1 promoter activity. The present study indicated that the expression level of Sirt1 was tightly regulated by oncoprotein c-Myc and tumor suppressor p53, which aids an improved understanding of its expression regulation and tumor promoter role in certain conditions. IntroductionSirtuin 1 (Sirt1), a conserved NAD + dependent deacetylase, has been implicated in modulating transcriptional silencing and cell survival, and is known to serve a role in tumorigene sis via deacetylation of important transcriptional factors, including tumor protein p53 (p53) (1), E2F transcription factor 1 (E2F1) (2) and nuclear factor-κB (3).Despite the paradoxical role of Sirt1 in tumorigenesis, the expression level of Sirt1 is increased in numerous types of cancer cell. Upregulation of Sirt1 is frequently observed in non-melanoma skin cancers, including actinic keratosis, Bowen's disease, squamous cell carcinoma and basal cell carcinoma (4). Sirt1 expression level is also significantly increased in poorly differentiated mouse and human prostate cancer (5), acute myeloid leukemia (AML) (6) and lymphoma (7).The expression level of Sirt1 is differentially regulated by oncogenes and tumor suppressor genes. p53 has been reported to repress the expression of Sirt1 and its removal by forkhead box O3 activated Sirt1 transcription in PC12 neuronal cancer cells (8,9). This model is further supported by studies investigating transformation-associated p53 knockout mice, which expressed constitutively higher Sirt1 mRNA expression levels in numerous tissues (10).Of note, hypermethylated in cancer 1 (HIC1), another tumor suppressor that acts as a repressor of Sirt1 expression level, formed a transcriptional repression complex with Sirt1, which induced inhibition of Sirt1 transcription (11). Sirt1 expression is regulated by the transcriptional factor E2F1, which binds two sites within the Sirt1 promoter. E2F1 is a crucial activator of Sirt1 expres...

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“…MYC deregulation due to gene amplification [8], [9], chromosomal translocation or insertion [10], [11], mutations [12], and epigenetic modifications [13], [14], has been reported in different types of cancers, especially in gastric cancer. MYC expression is often elevated or deregulated in human neoplasms [4], and seems to be at the crossroad of several important pathways and processes involved in carcinogenesis [15], being a key event in gastric carcinogenesis [9].…”

Section: Introductionmentioning

confidence: 99%

MYC Deregulation in Gastric Cancer and Its Clinicopathological Implications

et al. 2013

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Our study investigated the relationship between MYC alterations and clinicopathological features in gastric cancers. We evaluated the effect of MYC mRNA expression and its protein immunoreactivity, as well as copy number variation, promoter DNA methylation, and point mutations, in 125 gastric adenocarcinoma and 67 paried non-neoplastic tissues. We observed that 77% of the tumors presented MYC immunoreactivity which was significantly associated with increased mRNA expression (p<0.05). These observations were associated with deeper tumor extension and the presence of metastasis (p<0.05). MYC protein expression was also more frequently observed in intestinal-type than in diffuse-type tumors (p<0.001). Additionally, MYC mRNA and protein expression were significantly associated with its copy number (p<0.05). The gain of MYC copies was associated with late-onset, intestinal-type, advanced tumor stage, and the presence of distant metastasis (p<0.05). A hypomethylated MYC promoter was detected in 86.4% of tumor samples. MYC hypomethylation was associated with diffuse-type, advanced tumor stage, deeper tumor extension, and the presence of lymph node metastasis (p<0.05). Moreover, eighteen tumor samples presented at least one known mutation. The presence of MYC mutations was associated with diffuse-type tumor (p<0.001). Our results showed that MYC deregulation was mainly associated with poor prognostic features and also reinforced the presence of different pathways involved in intestinal-type and diffuse-type gastric carcinogenesis. Thus, our findings suggest that MYC may be a useful marker for clinical stratification and prognosis.

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Detection of C‐MYC oncogene translocation and copy number change in the normal‐dysplasia‐carcinoma sequence of the larynx by fluorescence in situ hybridization

Cited by 9 publications

References 29 publications

Over-expression of MEOX2 promotes apoptosis through inhibiting the PI3K/Akt pathway in laryngeal cancer cells

Over-expression of MEOX2 promotes apoptosis through inhibiting the PI3K/Akt pathway in laryngeal cancer cells

p53 inhibits the upregulation of sirtuin 1 expression induced by c-Myc

MYC Deregulation in Gastric Cancer and Its Clinicopathological Implications

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