De novo Identification of MIZ-1 (ZBTB17) Encoding a MYC-Interacting Zinc-Finger Protein as a New Favorable Neuroblastoma Gene

Ikegaki, Naohiko; Gotoh, Takahiro; Kung, Bing; Riceberg, Justin S.; Kim, David Y.; Zhao, Huaqing; Rappaport, Eric; Hicks, Sakeenah L.; Seeger, Robert C.; Tang, Xiaochao

doi:10.1158/1078-0432.ccr-07-0071

Cited by 20 publications

(21 citation statements)

References 29 publications

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“…We have previously reported that known favorable neuroblastoma genes are epigenetically silenced in unfavorable neuroblastoma cells (13). In addition, our study suggests that favorable neuroblastoma gene expressions can be considered molecular indicators of the effectiveness of chemotherapeutic agents against neuroblastoma cells (9).…”

Section: Introductionmentioning

confidence: 55%

“…Notably, MYCN-amplified neuroblastomas, the most aggressive form of the tumor, exhibit little or no expression of these genes. Thus far, several favorable neuroblastoma genes have been identified, which include EPHB6, EFNB2, EFNB3, NTRK1 (TrkA), CD44 and MIZ-1 (7)(8)(9)(10)(11)(12). We have previously reported that known favorable neuroblastoma genes are epigenetically silenced in unfavorable neuroblastoma cells (13).…”

Section: Introductionmentioning

confidence: 99%

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Hsp90 inhibition increases p53 expression and destabilizes MYCN and MYC in neuroblastoma

Regan

Jacobs²,

Wang³

et al. 2010

Int J Oncol

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Abstract. Neuroblastoma is a childhood cancer that exhibits either a favorable or an unfavorable phenotype. MYCN and MYC are oncoproteins that play crucial roles in determining the malignancy of unfavorable neuroblastoma. The Hsp90 superchaperone complex assists in the folding and function of a variety of oncogenic client proteins. Inhibition of Hsp90 by small molecule inhibitors leads to the destabilization of these oncogenic proteins and consequently suppresses tumor malignancy. Nonetheless, little is known about the effect of Hsp90 inhibition on the stability of MYCN and MYC proteins. In this study, we investigated the effect of Hsp90 inhibition on the phenotype of unfavorable neuroblastoma cells including its effect on MYCN and MYC expression. Two MYCN-amplified neuroblastoma cell lines (IMR5 and CHP134) and two non-MYCN-amplified cell lines (SY5Y and SKNAS) were used to address the effect of Hsp90 inhibition on the malignant phenotype of neuroblastoma. It was found that Hsp90 inhibition in neuroblastoma cell lines resulted in significant growth suppression, a decrease in MYCN and MYC expression, and an increase in the expression of p53. In the TP53-mutated SKNAS cell line, Hsp90 inhibition enhanced the expression of the favorable neuroblastoma genes EFNB2, . In addition, Hsp90 inhibition reduced HDAC6 expression and enhanced tubulin acetylation. Together our data suggest that Hsp90 inhibition suppresses the growth of neuroblastoma through multiple cellular pathways and that MYC/MYCN destabilization is among the important consequences of Hsp90 inhibition.

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Section: Introductionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Hsp90 inhibition increases p53 expression and destabilizes MYCN and MYC in neuroblastoma

Regan

Jacobs²,

Wang³

et al. 2010

Int J Oncol

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show abstract

“…In contrast, deletions of variable size and location within 1p36 are frequent in multiple human tumors, leading to the suggestion that the region contains several tumor suppressor genes (Bagchi and Mills 2008). One example is neuroblastoma and MIZ-1 has tumor-suppressor properties in this neoplasm (Ikegaki et al 2007). Mutations and SNPs close to the MIZ-1 gene have been associated with blindness and congenital heart failure.…”

Section: Human Tumorsmentioning

confidence: 99%

The Role of MIZ-1 in MYC-Dependent Tumorigenesis

Wiese

Walz

Eyß

et al. 2013

Cold Spring Harbor Perspectives in Medicine

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“…In fact, similar observations were previously made in genes residing in 1p36. These include ZBTB17 (MIZ-1) (29) and CHD5 (34,35).…”

Section: Discussionmentioning

confidence: 99%

“…shares several characteristics with favorable neuroblastoma genes (EPHB6, EFNB2, EFNB3, TrkA, CD44 and MIZ-1) (22,23,29). Their expression is low in neuroblastoma cell lines and can be enhanced by gene silencing inhibitors.…”

Section: Epha2 Expression Is Not Associated With Neuroblastoma Diseasmentioning

confidence: 99%

Biological significance of EPHA2 expression in neuroblastoma

et al. 2009

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Abstract. Neuroblastoma is a pediatric solid tumor that exhibits striking clinical bipolarity. Despite extensive efforts to treat unfavorable neuroblastoma, survival rate of children with the disease is among the lowest. Previous studies suggest that EPHA2, a member of the EPH family receptor kinases, can either promote or suppress cancer cell growth depending on cellular contexts. In this study, we investigated the biological significance of EPHA2 in neuroblastoma. It was found that tumorigenic N-type neuroblastoma cell lines expressed low levels of EPHA2, whereas hypo-tumorigenic S-type neuroblastoma cell lines expressed high levels of EPHA2 (p<0.005). Notably, inhibitors of DNA methylation and histone deacetylase enhanced EPHA2 expression in N-type cells, suggesting that EPHA2 is epigenetically silenced in unfavorable neuroblastoma cells. Furthermore, ectopic high-level expression of EPHA2 in N-type neuroblastoma cell lines resulted in significant growth suppression. However, Kaplan-Meier survival analysis showed that high EPHA2 expression was not associated with a good disease outcome of neuroblastoma, indicating that EPHA2 is not a favorable neuroblastoma gene, but a growth suppressive gene for neuroblastoma. Accordingly, EPHA2 expression was markedly augmented in vitro in neuroblastoma cells treated with doxorubicin, which is commonly used for treating unfavorable neuroblastoma. Taken together, EPHA2 is one of the effectors of chemotherapeutic agents (e.g., gene silencing inhibitors and DNA damaging agents). EPHA2 expression may thus serve as a biomarker of drug responsiveness for neuroblastoma during the course of chemotherapy. In addition, pharmaceutical enhancement of EPHA2 by non-cytotoxic agents may offer an effective therapeutic approach in the treatment of children with unfavorable neuroblastoma.

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De novo Identification of MIZ-1 (ZBTB17) Encoding a MYC-Interacting Zinc-Finger Protein as a New Favorable Neuroblastoma Gene

Cited by 20 publications

References 29 publications

Hsp90 inhibition increases p53 expression and destabilizes MYCN and MYC in neuroblastoma

Hsp90 inhibition increases p53 expression and destabilizes MYCN and MYC in neuroblastoma

The Role of MIZ-1 in MYC-Dependent Tumorigenesis

Biological significance of EPHA2 expression in neuroblastoma

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