Phosphorylation and stabilization of c-Myc by NEMO renders cells resistant to ionizing radiation through up-regulation of γ-GCS

Han, Young‐Hoon

doi:10.3892/or.2011.1432

Cited by 7 publications

(5 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 37 , 38 Overexpression of c-MYC has been associated with radiation resistance, which could confer a survival advantage during a fractioned therapeutic dosing regimen and could be an important phenotype required for cell transformation. 39 , 40 , 41 , 42 The application of targeted therapy against cells with dysregulated c-MYC expression 43 could therefore prove efficacious in the treatment of radiogenic breast cancer and might have value to prophylactically inhibit the outgrowth of c-MYC deregulated cells following radiation exposure.…”

Section: Discussionmentioning

confidence: 99%

c-MYC is a radiosensitive locus in human breast cells

et al. 2014

View full text Add to dashboard Cite

Ionising radiation is a potent human carcinogen. Epidemiological studies have shown that adolescent and young women are at increased risk of developing breast cancer following exposure to ionising radiation compared with older women, and that risk is dose-dependent. Although it is well understood which individuals are at risk of radiation-induced breast carcinogenesis, the molecular genetic mechanisms that underlie cell transformation are less clear. To identify genetic alterations potentially responsible for driving radiogenic breast transformation, we exposed the human breast epithelial cell line MCF-10A to fractionated doses of X-rays and examined the copy number and cytogenetic alterations. We identified numerous alterations of c-MYC that included high-level focal amplification associated with increased protein expression. c-MYC amplification was also observed in primary human mammary epithelial cells following exposure to radiation. We also demonstrate that the frequency and magnitude of c-MYC amplification and c-MYC protein expression is significantly higher in breast cancer with antecedent radiation exposure compared with breast cancer without a radiation aetiology. Our data also demonstrate extensive intratumor heterogeneity with respect to c-MYC copy number in radiogenic breast cancer, suggesting continuous evolution at this locus during disease development and progression. Taken together, these data identify c-MYC as a radiosensitive locus, implicating this oncogenic transcription factor in the aetiology of radiogenic breast cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

c-MYC is a radiosensitive locus in human breast cells

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Second, the suppression of c-Myc might also contribute to the decreased radiation resistance in CD133 + Mahlavu CSCs. It has been shown that the modulation of c-Myc leads to radiation sensitization of hepatoma cells [19, 20]. Furthermore, our unpublished data showed that PT treatment could suppress another major molecule, survivin, which has been implicated for radiation resistance in glioma [21].…”

Section: Discussionmentioning

confidence: 99%

BlueBerry Isolate, Pterostilbene, Functions as a Potential Anticancer Stem Cell Agent in Suppressing Irradiation-Mediated Enrichment of Hepatoma Stem Cells

Lee

Huynh

et al. 2013

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

For many malignancies, radiation therapy remains the second option only to surgery in terms of its curative potential. However, radiation-induced tumor cell death is limited by a number of factors, including the adverse response of the tumor microenvironment to the treatment and either intrinsic or acquired mechanisms of evasive resistance, and the existence of cancer stem cells (CSCs). In this study, we demonstrated that using different doses of irradiation led to the enrichment of CD133+ Mahlavu cells using flow cytometric method. Subsequently, CD133+ Mahlavu cells enriched by irradiation were characterized for their stemness gene expression, self-renewal, migration/invasion abilities, and radiation resistance. Having established irradiation-enriched CD133+ Mahlavu cells with CSC properties, we evaluated a phytochemical, pterostilbene (PT), found abundantly in blueberries, against irradiation-enriched CSCs. It was shown that PT treatment dose-dependently reduced the enrichment of CD133+ Mahlavu cells upon irradiation; PT treatment also prevented tumor sphere formation, reduced stemness gene expression, and suppressed invasion and migration abilities as well as increasing apoptosis of CD133+ Mahlavu CSCs. Based on our experimental data, pterostilbene could be used to prevent the enrichment of CD133+ hepatoma CSCs and should be considered for future clinical testing as a combined agent for HCC patients.

show abstract

“…Furthermore, c-Myc amplification not only contributes to the genesis and progression of most human tumors, but affects the outcome of cancer radio- or chemotherapy1112. Indeed, a series of reports have demonstrated that the overexpression of c-Myc contributed to cancer radioresistance1314151617. Thus, targeting c-Myc could be a potential strategy against prostate cancer.…”

mentioning

confidence: 99%

MicroRNA-449a enhances radiosensitivity by downregulation of c-Myc in prostate cancer cells

Mao

Zhao

Zhou

et al. 2016

Sci Rep

View full text Add to dashboard Cite

MicroRNAs (miRNAs) have been reported to be involved in DNA damage response induced by ionizing radiation (IR). c-Myc is reduced when cells treated with IR or other DNA damaging agents. It is unknown whether miRNAs participate in c-Myc downregulation in response to IR. In the present study, we found that miR-449a enhanced radiosensitivity in vitro and in vivo by targeting c-Myc in prostate cancer (LNCaP) cells. MiR-449a was upregulated and c-Myc was downregulated in response to IR in LNCaP cells. Overexpression of miR-449a or knockdown of c-Myc promoted the sensitivity of LNCaP cells to IR. By establishing c-Myc as a direct target of miR-449a, we revealed that miR-449a enhanced radiosensitivity by repressing c-Myc expression in LNCaP cells. Furthermore, we showed that miR-449a enhanced radiation-induced G2/M phase arrest by directly downregulating c-Myc, which controlled the Cdc2/CyclinB1 cell cycle signal by modulating Cdc25A. These results highlight an unrecognized mechanism of miR-449a-mediated c-Myc regulation in response to IR and may provide alternative therapeutic strategies for the treatment of prostate cancer.

show abstract

Phosphorylation and stabilization of c-Myc by NEMO renders cells resistant to ionizing radiation through up-regulation of γ-GCS

Cited by 7 publications

References 19 publications

c-MYC is a radiosensitive locus in human breast cells

c-MYC is a radiosensitive locus in human breast cells

BlueBerry Isolate, Pterostilbene, Functions as a Potential Anticancer Stem Cell Agent in Suppressing Irradiation-Mediated Enrichment of Hepatoma Stem Cells

MicroRNA-449a enhances radiosensitivity by downregulation of c-Myc in prostate cancer cells

Contact Info

Product

Resources

About