Role of Tumor Necrosis Factor-α and TRAIL in High-Dose Radiation–Induced Bystander Signaling in Lung Adenocarcinoma

Shareef, Mohammed M.; Cui, Nuan; Burikhanov, Ravshan; Gupta, Seema; Satishkumar, Sabapathi; Shajahan, Shahin; Mohiuddin, Mohammed; Rangnekar, Vivek M.; Ahmed, Mansoor M.

doi:10.1158/0008-5472.can-07-0722

Cited by 117 publications

(84 citation statements)

References 48 publications

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“…In tumor cell lines and tumors representing prostate, kidney and gastric cancer, EGR1 stimulated tumor cell growth and was associated with a poor prognosis (15,16). By contrast, in fibrosarcoma, glioblastoma, melanoma and esophageal lung and breast cancer, EGR1 is reported to be a tumor suppressor (7,8,(17)(18)(19)(20). Of the head and neck cancers, only in nasopharyngeal carcinoma was it found that the expression of EGR1 had a positive prognostic effect on survival (21).…”

Section: Discussionmentioning

confidence: 99%

EGR1 regulates radiation-induced apoptosis in head and neck squamous cell carcinoma

et al. 2015

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Abstract. The transcription factor, early growth response 1 (EGR1) belongs to the early growth response family. EGR1 regulates the transactivation of genes involved in growth inhibition and apoptosis by ionizing radiation. The aims of the present study were to evaluate the expression of EGR1, and its relationship to prognosis, in patients with advanced laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) receiving chemoradiation therapy, and to observe the effect of EGR1 on the apoptosis of head and neck squamous cell carcinoma (HNSCC) cells treated with ionizing radiation. Expression of the EGR1 protein in tissue samples from patients with LHSCC was detected by immunohistochemistry. A high expression of the EGR1 protein was observed in 37 (67.3%) of the 55 LHSCC tissue samples examined. A high EGR1 protein expression in patients with LHSCC who were treated with chemoradiation was significantly associated with improved larynx-preservation survival (p=0.04). The 5-year diseasespecific survival rate with larynx preservation was 59% in patients with a high EGR1 protein expression vs. 30% in those with a low EGR1 protein expression. In the human HNSCC cell line, PCI50, EGR1 mRNA expression was induced at 30-60 min, and EGR1 protein expression was induced at 60-120 min, after exposure to a 5 Gy dose of ionizing radiation. To evaluate the impact of EGR1 on radiation-induced apoptosis, we used small-interfering RNA to knock down endogenous EGR1 gene expression. Cleaved caspase 3, cleaved caspase 7, and cleaved PARP were decreased, while XIAP was increased, in EGR1-knockdown PCI50 cells compared to negative control PCI50 cells, at all observed post-irradiation time points. These findings suggested that EGR1 knockdown inhibits radiation-induced apoptosis. In conclusion, EGR1 may be associated with larynx-preservation survival, through the regulation of radiation-induced apoptosis in patients with LHSCC treated with chemoradiation. Although further investigations are required to support the present study, EGR1 serves as a favorable biomarker of radiosensitivity in the treatment of LHSCC.

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Section: Discussionmentioning

confidence: 99%

EGR1 regulates radiation-induced apoptosis in head and neck squamous cell carcinoma

et al. 2015

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“…Chromatin immunoprecipitation assay was described earlier (Shareef et al, 2007) using 2-5 Â 10 9 PC3 cells. PCR was performed using specific primers for BAX promoter (5 0 -GC CTGGGCAACACAGTGAG-3 0 and 5 0 -GCTCCCTCGGGA GGTTTG-3 0 ) that yielded B500 bp product.…”

Section: Chromatin Immunoprecipitationmentioning

confidence: 99%

EGR-1 forms a complex with YAP-1 and upregulates Bax expression in irradiated prostate carcinoma cells

et al. 2009

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In this study, we investigated the functional role of early growth response-1 (Egr1 gene) in the regulation of radiation-induced clonogenic inhibition and apoptosis in p53 wild-type and mutant prostate cancer cells 22Rv1 and DU145, respectively. 22Rv1 cells were more sensitive to irradiation compared with DU145 cells, and the sensitivity was enhanced by overexpression of EGR-1 in both cells. Dominant-negative EGR-1 mutant (dnEGR-1) or repressor of EGR-1, NGFIA binding protein 1 (NAB1), increased radioresistance of these cells. Significant activation of caspases 3 and 9 and Bcl2-associated X (Bax) with increased poly(ADP-ribose) polymerase (PARP) cleavage and cytochrome c release was observed in radiation-exposed EGR-1 overexpressing cells. Gel shift analysis and chloramphenicol acetyl transferase (CAT) reporter assays indicate that EGR-1 transactivates the promoter of the Bax gene. Interaction of EGR-1 and Yes kinase-associated protein 1 (YAP-1) through the WW domain of YAP-1 enhances the transcriptional activity of EGR-1 on the Bax promoter as shown by chromatin immunoprecipitation and reporter assays. Irradiation of PC3 cell xenografts that were treated with adenoviral EGR-1 showed significant regression in tumor volume. These findings establish the radiation-induced pro-apoptotic action of EGR-1, in a p53-independent manner, by directly transactivating Bax, and prove that alters the B-cell CLL/ lymphoma 2 (Bcl-2)/Bax ratio as one of the mechanisms resulting in significant activation of caspases, leading to cell death through the novel interaction of EGR-1 with YAP-1.

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“…Bystander signals may be transferred to surrounding cells either by gap junctional intercellular communication or by the production of soluble extracellular factors released from irradiated cells. Soluble signaling factors such as reactive oxygen species (ROS) (8)(9)(10)(11)(12), nitric oxide (NO) (12)(13)(14), secondary messengers like calcium (4,(8)(9)(10), cytokines such as interleukins (15)(16)(17), TGFb (18,19), TNFa and TRAIL (20,21) have been found to play a major role in radiation-induced bystander effects. A new mechanism for communication by soluble factors could be by intercellular communication by exosomes.…”

Section: Introductionmentioning

confidence: 99%

Exosomes Are Involved in Mediating Radiation Induced Bystander Signaling in Human Keratinocyte Cells

Jella¹,

et al. 2014

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Role of Tumor Necrosis Factor-α and TRAIL in High-Dose Radiation–Induced Bystander Signaling in Lung Adenocarcinoma

Cited by 117 publications

References 48 publications

EGR1 regulates radiation-induced apoptosis in head and neck squamous cell carcinoma

EGR1 regulates radiation-induced apoptosis in head and neck squamous cell carcinoma

EGR-1 forms a complex with YAP-1 and upregulates Bax expression in irradiated prostate carcinoma cells

Exosomes Are Involved in Mediating Radiation Induced Bystander Signaling in Human Keratinocyte Cells

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