Overexpression of immediate early gene X‐1 (IEX‐1) enhances γ‐radiation‐induced apoptosis of human glioma cell line, U87‐MG

Yamashita, Kentaro; You, Fukka; Hayashi, Shinichiro; Iwama, Toru

doi:10.1111/j.1440-1789.2008.00932.x

Cited by 9 publications

(4 citation statements)

References 23 publications

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“…Its transcription is regulated by p53, Sp1, c-Myc, and NF-κB in a synergistic or opposing manner in different cells 14 15 16 . IER3 regulates multiple cellular processes, including apoptosis 17 18 19 20 , proliferation 21 22 , differentiation 21 23 , and DNA repair 24 , and its response varies depending on cellular context. Although the mechanism underlying the IER3-mediated induction of apoptosis is not clearly understood at present, its involvement with the BCL-2 family, which is the pivotal regulator of cell survival and death, has been demonstrated; the presence of functional BIM is required for IER3-induced apoptosis.…”

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confidence: 99%

IER3 is a crucial mediator of TAp73β-induced apoptosis in cervical cancer and confers etoposide sensitivity

Jin

Suh

Kim

et al. 2015

Sci Rep

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Infection with high-risk human papillomaviruses (HPVs) causes cervical cancer. E6 oncoprotein, an HPV gene product, inactivates the major gatekeeper p53. In contrast, its isoform, TAp73β, has become increasingly important, as it is resistant to E6. However, the intracellular signaling mechanisms that account for TAp73β tumor suppressor activity in cervix are poorly understood. Here, we identified that IER3 is a novel target gene of TAp73β. In particular, TAp73β exclusively transactivated IER3 in cervical cancer cells, whereas p53 and TAp63 failed to do. IER3 efficiently induced apoptosis, and its knockdown promoted survival of HeLa cells. In addition, TAp73β-induced cell death, but not p53-induced cell death, was inhibited upon IER3 silencing. Moreover, etoposide, a DNA-damaging chemotherapeutics, upregulated TAp73β and IER3 in a c-Abl tyrosine kinase-dependent manner, and the etoposide chemosensitivity of HeLa cells was largely determined by TAp73β-induced IER3. Of interest, cervical carcinomas from patients express no observable levels of two proteins. Thus, our findings suggest that IER3 is a putative tumor suppressor in the cervix, and the c-Ab1/p73β/IER3 axis is a novel and crucial signaling pathway that confers etoposide chemosensitivity. Therefore, TAp73β and IER3 induction would be a valuable checkpoint for successful therapeutic intervention of cervical carcinoma patients.

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confidence: 99%

IER3 is a crucial mediator of TAp73β-induced apoptosis in cervical cancer and confers etoposide sensitivity

Jin

Suh

Kim

et al. 2015

Sci Rep

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“…The expression levels of these genes were correlated with each other, and the 16-fold dilution of PAM elevated these genes to the highest level. Rho family GTPase ( RND3 , also known as RhoE ), Cation transport regulator-like protein ( CHAC1 ), and Immediate early response ( IER3 , also known as IEX1 ), which also induce apoptosis in glioblastoma cells 48–50 , were ranked in the top 10 (Fig. 4c).…”

Section: Resultsmentioning

confidence: 99%

“…Temozolomide, which is a chemotherapeutic drug for treatment of glioblastoma, highly upregulates CHAC1 , and overexpression of CHAC1 significantly influences temozolomide-mediated apoptosis in glioblastoma 49 . Overexpression of IER3 sensitizes glioblastoma cells to γ-radiation-induced apoptosis 50 . These three genes ( RND3 , CHAC1 , and IER3 ) were ranked in the top 10 genes that were upregulated by PAM.…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress-dependent and -independent death of glioblastoma cells induced by non-thermal plasma-exposed solutions

Tanaka

Mizuno

Katsumata

et al. 2019

Sci Rep

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Non-thermal atmospheric pressure plasma has been widely used for preclinical studies in areas such as wound healing, blood coagulation, and cancer therapy. We previously developed plasma-activated medium (PAM) and plasma-activated Ringer’s lactate solutions (PAL) for cancer treatments. Many in vitro and in vivo experiments demonstrated that both PAM and PAL exhibit anti-tumor effects in several types of cancer cells such as ovarian, gastric, and pancreatic cancer cells as well as glioblastoma cells. However, interestingly, PAM induces more intracellular reactive oxygen species in glioblastoma cells than PAL. To investigate the differences in intracellular molecular mechanisms of the effects of PAM and PAL in glioblastoma cells, we measured gene expression levels of antioxidant genes such as CAT, SOD2, and GPX1. Microarray and quantitative real-time PCR analyses revealed that PAM elevated stress-inducible genes that induce apoptosis such as GADD45α signaling molecules. PAL suppressed genes downstream of the survival and proliferation signaling network such as YAP/TEAD signaling molecules. These data reveal that PAM and PAL induce apoptosis in glioblastoma cells by different intracellular molecular mechanisms.

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“…Unfortunately, the tumor cells are usually resistant to irradiation or chemotherapy. Overexpression of IEX-1 in HeLa cells enhanced their sensitivity to apoptosis induced by chemotherapeutic agent [78] and overexpression of IEX-1 also sensitized human glioma cell lines to apoptosis induced by irradiation [79]. Thus, IEX-1 may be a candidate gene for enhancing the efficacy of radiotherapy or chemotherapy.…”

Section: Expert Opinionmentioning

confidence: 99%

Immediate early response gene X-1, a potential prognostic biomarker in cancers

Ustyugova

Liang

et al. 2013

Expert Opinion on Therapeutic Targets

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Introduction The immediate early response gene X-1 (IEX-1) plays a pivotal role in the regulation of cell apoptosis, proliferation, differentiation and metabolism. Deregulation of IEX-1 expression has been confirmed in multiple cancers in humans, in association with either poor or better prognosis depending on the type and progression stages of the cancer. Areas covered This review summarizes clinical studies of altered IEX-1 expression in ovarian, pancreatic, blood, breast and colorectal cancers, lymphoma and myeloma. The authors also outline the current understandings of the complex functions of IEX-1 gained from studies with animal models and tumor cell lines so as to help us comprehend the significance of the clinical findings. Expert opinion IEX-1 holds great promise to be a valuable biomarker, either alone or in combination with other genes, for monitoring progression of some cancers. IEX-1 expression is highly sensitive to environmental cues and distinct between normal and cancer cells. However, use of IEX-1 as a biomarker remains a significant challenge because too little is understood about the mechanism underlying the diverse activities of IEX-1 and a standardized clinical assay for IEX-1 detection and validation of clinical results across different studies are still critically lacking.

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Overexpression of immediate early gene X‐1 (IEX‐1) enhances γ‐radiation‐induced apoptosis of human glioma cell line, U87‐MG

Cited by 9 publications

References 23 publications

IER3 is a crucial mediator of TAp73β-induced apoptosis in cervical cancer and confers etoposide sensitivity

IER3 is a crucial mediator of TAp73β-induced apoptosis in cervical cancer and confers etoposide sensitivity

Oxidative stress-dependent and -independent death of glioblastoma cells induced by non-thermal plasma-exposed solutions

Immediate early response gene X-1, a potential prognostic biomarker in cancers

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