NFκB activity and transcriptional responses in human breast adenocarcinoma cells after single and fractionated irradiation

Madhusoodhanan, Rakhesh; Natarajan, Mohan; Veeraraghavan, Jamunarani; Herman, Terence S.; Aravindan, Natarajan

doi:10.4161/cbt.8.9.8105

Cited by 26 publications

(23 citation statements)

References 51 publications

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“…NF-jB is a transcription factor that promotes the expression of genes involved in inflammatory and antiapoptotic response [37][38][39][40]. It has been demonstrated that NF-jB plays a critical role in development and progression of breast cancer [41][42][43]. Furthermore, it has been proposed that BRCA1 acts as a co-activator of NF-jB [44].…”

Section: Discussionmentioning

confidence: 99%

Integration of BRCA1-mediated miRNA and mRNA profiles reveals microRNA regulation of TRAF2 and NFκB pathway

Tanić

Zając

Gómez‐López

et al. 2011

Breast Cancer Res Treat

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Microarray-based techniques are being useful to obtain miRNA and gene expression signatures associated with different tumors. BRCA1 deregulation is a frequent event in the pathogenesis of breast as well as other cancers. In addition to DNA repair functions of BRCA1, it is involved in a wide range of cellular processes such as cell cycle, chromatin remodeling or transcription. However, the molecular events underlying BRCA1-associated tumorigenesis are still largely unknown. In order to deepen our understanding of BRCA1-associated tumorigenesis, we integrated data from mRNA and miRNA microarray experiments on HCC1937 breast cancer cell line, and the isogenic HCC1937 stably expressing BRCA1, to obtain significant miRNA-mRNA relationships associated with the presence of BRCA1 gene. By using bioinformatic integration of gene and miRNA expression data, we found significant miRNA-gene relationships underlying the array signatures. We additionally evaluated the role of these statistically significant pairs at the biological pathways level and identified MAPK and NF-κB pathways associated with these expression changes. Furthermore, we experimentally validated miRNAs induced by BRCA1 that commonly regulate TRAF2, a key regulator of NF-κB and MAPK pathways. We demonstrate that miR-146a, miR-99b and miR-205, induced in HCC1937 BRCA1-expressing cells, bind and regulate TRAF2 gene. In addition, re-expression of miR-146a, miR-99b or miR-205 in HCC1937 BRCA1-null cells was sufficient to modulate NF-κB activity. Our results demonstrate that integration of mRNA and miRNA associated with BRCA1 expression was useful to discover new miRNA-gene interactions as molecular events underlying BRCA1-mediated tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

Integration of BRCA1-mediated miRNA and mRNA profiles reveals microRNA regulation of TRAF2 and NFκB pathway

Tanić

Zając

Gómez‐López

et al. 2011

Breast Cancer Res Treat

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“…38,41 Irradiation also can activate NF-kB survival transcription factor via degradation of IkBa. 42,43 The radiation-induced activation of HIF-1a and NF-kB has been proposed as dominant governor triggering radioprotection of tumor vessels and critical determinant of radioresistance. ING4 can potentially inhibit the transcriptional activity of NF-kB and HIF-1a leading to the inhibition of production of proangiogenic factors.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, AdVING4 almost completely eliminated the increased Cox-2 and survivin induced by ionizing radiation. It has been shown that ionizing radiation can enhance the transcriptional activity of NF-kB 42,43 and HIF-1a 38 and positively modulate the expression of downstream genes Cox-2 47,48 and survivin. 49,50 It has also been reported that ING4 can efficiently suppress the activity of NF-kB and HIF-1a.…”

Section: Discussionmentioning

confidence: 99%

Enhanced radiosensitivity of non-small-cell lung cancer (NSCLC) by adenovirus-mediated ING4 gene therapy

et al. 2012

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Radiotherapy is the common treatment of choice for locally advanced lung cancer, but the radioresistance of lung cancer remains a significant therapeutic obstacle. We previously demonstrated that adenovirus-mediated inhibitor of growth 4 (ING4) tumor suppressor gene delivery (AdVING4) can chemosensitize human hepatocarcinoma cells to anticancer drug cisplatin (CDDP). However, its radiosensitizing effects in cancer therapy are largely elusive. In the present study, we investigated the therapeutic efficacy of AdVING4 gene therapy combined with ionizing radiotherapy for SPC-A1 human non-small-cell lung cancer (NSCLC) cells in vitro and in vivo in athymic nude mice, and also elucidated its underlying mechanisms. We found that AdVING4 gene therapy plus radiotherapy induced synergistic tumor suppression and apoptosis in in vitro SPC-A1 human NSCLC cells and in vivo SPC-A1 xenografted tumors s.c. implanted in athymic nude mice. Mechanistically, AdVING4 combined with radiation resulted in a substantial upregulation of Bax, Fas, FasL and Cleaved Caspase-3, and downregulation of Bcl-2 in SPC-A1 human NSCLC xenografted tumors. In addition, AdVING4 plus radiation synergistically reduced the tumor vessel CD34 expression and microvessel density (MVD) in vivo. Most importantly, AdVING4 potentially blocked the radiation-induced enhancement of cyclooxygenase-2 and survivin radioresistant factors, and vascular endothelial growth factor and IL-8 proangiogenic factors. The enhanced antitumor effects elicited by AdVING4 plus radiotherapy were closely associated with the cooperative activation of intrinsic and extrinsic apoptotic pathways, and synergistic inhibition of tumor angiogenesis. Thus, our results suggested that AdVING4 combined with radiotherapy may be a feasible and effective strategy for treatment of radioresistant NSCLC and other cancers.

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“…Radiotherapy is considered mandatory for glioblastoma patients [2] . However, the development of radioresistance remains a significant therapeutic hindrance and limits the effectiveness of ionizing radiation (IR) in treating patients with glioma [1,3] .…”

Section: Introductionmentioning

confidence: 99%

Inhibition of cathepsin L sensitizes human glioma cells to ionizing radiation in vitro through NF-κB signaling pathway

Yang

Wang

et al. 2015

Acta Pharmacol Sin

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Aim: Cathepsin L, a lysosomal cysteine proteinase, is exclusively elevated in a variety of malignancies, including gliomas. In this study we investigated the relationship between cathepsin L and NF-κB, two radiation-responsive elements, in regulating the sensitivity of human glioma cells ionizing radiation (IR) in vitro. Methods: Human glioma U251 cells were exposed to IR (10 Gy), and the expression of cathepsin L and NF-κB was measured using Western blotting. The nuclear translocation of NF-κB p65 and p50 was analyzed with immunofluorescence assays. Cell apoptosis was examined with clonogenic assays. NF-κB transcription and NF-κB-dependent cyclin D1 and ATM transactivation were monitored using luciferase reporter and ChIP assays, respectively. DNA damage repair was investigated using the comet assay.

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NFκB activity and transcriptional responses in human breast adenocarcinoma cells after single and fractionated irradiation

Cited by 26 publications

References 51 publications

Integration of BRCA1-mediated miRNA and mRNA profiles reveals microRNA regulation of TRAF2 and NFκB pathway

Integration of BRCA1-mediated miRNA and mRNA profiles reveals microRNA regulation of TRAF2 and NFκB pathway

Enhanced radiosensitivity of non-small-cell lung cancer (NSCLC) by adenovirus-mediated ING4 gene therapy

Inhibition of cathepsin L sensitizes human glioma cells to ionizing radiation in vitro through NF-κB signaling pathway

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