EGR-1 Induction Is Required for Maximal Radiosensitivity in A375-C6 Melanoma Cells

Ahmed, Mansoor M.; Venkatasubbarao, Kolaparthi; Fruitwala, Sana M.; Muthukkumar, Subramanian; Wood, David P.; Sells, Stephen F.; Mohiuddin, Mohammed; Rangnekar, Vivek M.

doi:10.1074/jbc.271.46.29231

Cited by 63 publications

(68 citation statements)

References 20 publications

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“…On the contrary, EGR-1 can suppress growth when overexpressed or re-expressed in transformed cells. EGR-1 can induce apoptosis either by stimulating p53 activity or by IR (Ahmed et al, 1996(Ahmed et al, , 1997, or PTEN expression (Virolle et al, 2001). Thus, it appears that EGR-1 can act as a tumor suppressor in some cells and as a growth stimulator in other cell types.…”

Section: Discussionmentioning

confidence: 99%

“…EGR-1 protein upregulates p53 in response to thapsigargin-induced apoptotic stimuli (Nair et al, 1997). Expression of dominant-negative EGR-1 mutant (dnEGR-1) in melanoma cells (wt p53) caused radio resistance (Ahmed et al, 1996). Despite the absence of p53 protein, the cells overexpressing EGR-1 protein were sensitive to IR, which was associated with upregulation of tumor necrosis factor-a protein through EGR-1-mediated transactivation (Ahmed et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

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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“…Quantitation of Apoptosis-To quantitate apoptosis, the ApopTag in situ apoptosis detection kit (Oncor) was used as described (45). The ApopTag kit detects the DNA strand breaks in single cells by terminal transferase-mediated dUTP-digoxigenin end labeling (TUNEL).…”

Section: Methodsmentioning

confidence: 99%

Restoration of Transforming Growth Factor-β Signaling Enhances Radiosensitivity by Altering the Bcl-2/Bax Ratio in the p53 Mutant Pancreatic Cancer Cell Line MIA PaCa-2

Ahmed

Alcock

Damodaran³

et al. 2002

Journal of Biological Chemistry

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In this study, we investigated whether lack of transforming growth factor ␤ (TGF-␤) type II receptor (RII) expression and loss of TGF-␤ signaling played a role in radiation resistance of pancreatic cancer cells MIA PaCa-2 that possess a mutated p53 gene. Transfection of this cell line with a RII cDNA led to a stimulation of the transcriptional activity of p3TP-Lux, a TGF-␤؊respon-sive reporter construct. The RII transfectants (MIA PaCa-2/RII) showed a significant increase in sensitivity to radiation when compared with MIA PaCa-2/vector cells. The increase in sensitivity to radiation was reversed by neutralizing antibodies to TGF-␤, indicating that these changes were dependent on TGF-␤ signaling.

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“…One g of total RNA was reverse-transcribed into cDNA using oligo(dT) primers and reverse transcriptase in a 40-l reaction mix as described previously (35). Radiation-induced mRNA expression of p53, p21…”

Section: P-reverse Transcriptase-polymerase Chain Reaction ( P-rt-pcrmentioning

confidence: 99%

“…In our previous report, using melanoma cells, which contain wild type p53, a dose-dependent increase in EGR-1 expression with dosedependent growth inhibition was observed when exposed to ionizing radiation (35). Transfectant melanoma cells stably expressing the dominant-negative mutant protein of EGR-1 showed significantly reduced (Ͻ50%) sensitivity to radiationinducible growth inhibition, and this resistance was found to be dose-dependent.…”

mentioning

confidence: 99%

Ionizing Radiation Down-regulates p53 Protein in Primary Egr-1−/− Mouse Embryonic Fibroblast Cells Causing Enhanced Resistance to Apoptosis

Das¹,

Damodaran²,

Dey³

et al. 2001

Journal of Biological Chemistry

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EGR-1 Induction Is Required for Maximal Radiosensitivity in A375-C6 Melanoma Cells

Cited by 63 publications

References 20 publications

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

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

Restoration of Transforming Growth Factor-β Signaling Enhances Radiosensitivity by Altering the Bcl-2/Bax Ratio in the p53 Mutant Pancreatic Cancer Cell Line MIA PaCa-2

Ionizing Radiation Down-regulates p53 Protein in Primary Egr-1−/− Mouse Embryonic Fibroblast Cells Causing Enhanced Resistance to Apoptosis

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