Expression of DNA-PKcs and BRCA1 as prognostic indicators in nasopharyngeal carcinoma following intensity-modulated radiation therapy

Yang, Jing; Xu, Ximing; Hao, Yanrong; Chen, Jiaxin; Lu, Hongsheng; Qin, Jian; Peng, Luxing; Chen, Biao

doi:10.3892/ol.2013.1196

Cited by 14 publications

(11 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We identified additional DNA repair factors, notably BRCA1 and DNA-PKcs which were significantly upregulated basally in A549 CD133+ cells and could also serve as promising CSC specific therapeutic targets. While their targeting has been proposed in multiple cancer models, their efficacy in inducing radiosensitivity in CSCs has largely yet to be explored [31–33]. …”

Section: Discussionmentioning

confidence: 99%

CD133+ cells contribute to radioresistance via altered regulation of DNA repair genes in human lung cancer cells

Desai

Webb

Gerson

2014

Radiotherapy and Oncology

104

View full text Add to dashboard Cite

Background Radioresistance in human tumors has been linked in part to a subset of cells termed cancer stem cells (CSCs). The prominin 1 (CD133) cell surface protein is proposed to be a marker enriching for CSCs. We explore the importance of DNA repair in contributing to radioresistance in CD133+ lung cancer cells. Materials and Methods A549 and H1299 lung cancer cell lines were used. Sorted CD133+ cells were exposed to either single 4Gy or 8Gy doses and clonogenic survival measured. γ-H2AX immunofluorescence and quantitative real time PCR was performed on sorted CD133+ cells both in the absence of IR and after two single 4Gy doses. Lentiviral shRNA was used to silence repair genes. Results A549 but not H1299 cells expand their CD133+ population after single 4Gy exposure, and isolated A549 CD133+ cells demonstrate IR resistance. This resistance corresponded with enhanced repair of DNA double strand breaks (DSBs) and upregulated expression of DSB repair genes in A549 cells. Prior IR exposure of two single 4Gy doses resulted in acquired DNA repair upregulation and improved repair proficiency in both A549 and H1299. Finally Exo1 and Rad51 silencing in A549 cells abrogated the CD133+ IR expansion phenotype and induced IR sensitivity in sorted CD133+ cells. Conclusions CD133 identifies a population of cells within specific tumor types containing altered expression of DNA repair genes that are inducible upon exposure to chemotherapy. This altered gene expression contributes to enhanced DSB resolution and the radioresistance phenotype of these cells. We also identify DNA repair genes which may serve as promising therapeutic targets to confer radiosensitivity to CSCs.

show abstract

Section: Discussionmentioning

confidence: 99%

CD133+ cells contribute to radioresistance via altered regulation of DNA repair genes in human lung cancer cells

Desai

Webb

Gerson

2014

Radiotherapy and Oncology

104

View full text Add to dashboard Cite

show abstract

“…There is also evidence that decreased DNA-PKcs expression can also drive tumor progression. Breast cancer patients with lower DNA-PKcs levels tended to have a higher rate of distant metastases and poorer prognosis [ 181 ]. The DNA-PKcs activity in the PBLs of patients with advanced cancer was determined to be significantly lower than in patients at an earlier cancer stage, and those patients had lower rates of disease free and distant metastasis free survival [ 182 ].…”

Section: Core Nhej Factors In Carcinogenesis and Cancermentioning

confidence: 99%

“…Ku80 is overexpressed in half of all HNSCC tumors analyzed in a study Moeller, B.J., et al, and it was found to be an independent predictor for both locoregional failure and mortality following radiotherapy [ 193 ]. Increased DNA-PKcs expression predicted poor outcome in nasopharyngeal carcinoma patients undergoing intensity modulated radiation therapy (IMRT), independent of classical markers [ 181 ]. DNA-PKcs also promotes radiation resistance in cervical and breast cancers as well as correlating with radioresistance in lung cancer lines [ 194 , 195 , 196 ].…”

Section: Core Nhej Factors In Carcinogenesis and Cancermentioning

confidence: 99%

The Role of the Core Non-Homologous End Joining Factors in Carcinogenesis and Cancer

Sishc

Davis

2017

Cancers

139

View full text Add to dashboard Cite

DNA double-strand breaks (DSBs) are deleterious DNA lesions that if left unrepaired or are misrepaired, potentially result in chromosomal aberrations, known drivers of carcinogenesis. Pathways that direct the repair of DSBs are traditionally believed to be guardians of the genome as they protect cells from genomic instability. The prominent DSB repair pathway in human cells is the non-homologous end joining (NHEJ) pathway, which mediates template-independent re-ligation of the broken DNA molecule and is active in all phases of the cell cycle. Its role as a guardian of the genome is supported by the fact that defects in NHEJ lead to increased sensitivity to agents that induce DSBs and an increased frequency of chromosomal aberrations. Conversely, evidence from tumors and tumor cell lines has emerged that NHEJ also promotes chromosomal aberrations and genomic instability, particularly in cells that have a defect in one of the other DSB repair pathways. Collectively, the data present a conundrum: how can a single pathway both suppress and promote carcinogenesis? In this review, we will examine NHEJ’s role as both a guardian and a disruptor of the genome and explain how underlying genetic context not only dictates whether NHEJ promotes or suppresses carcinogenesis, but also how it alters the response of tumors to conventional therapeutics.

show abstract

“…Enhanced DNA repair activity tends to be resistant to radiotherapy. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and ataxia telangiectasia-mutated are two members of the PI3K family that repair DNA DSBs (97)(98)(99). Inhibition of PI3 kinases using a pharmacological approach may improve the response of cancer cells to radiotherapy.…”

Section: Pi3k/akt and The Cell Cycle In Radiation Resistancementioning

confidence: 99%

Roles of glucose transporter-1 and the phosphatidylinositol 3-kinase/protein kinase B pathway in cancer radioresistance (Review)

Jin

Zhou

Fan

et al. 2014

Molecular Medicine Reports

View full text Add to dashboard Cite

The mechanisms underlying cancer radioresistance remain unclear. Several studies have found that increased glucose transporter‑1 (GLUT‑1) expression is associated with radioresistance. Recently, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway was reported to be involved in the control of GLUT‑1 trafficking and activity. Activation of the PI3K/Akt pathway may itself be associated with cancer radioresistance. Thus, increasing attention has been devoted to the effects of modifying the expression of GLUT‑1 and the PI3K/Akt pathway on the increase in the radiosensitivity of cancer cells. This review discusses the importance of the association between elevated expression of GLUT‑1 and activation of the PI3K/Akt pathway in the development of radioresistance in cancer.

show abstract

Expression of DNA-PKcs and BRCA1 as prognostic indicators in nasopharyngeal carcinoma following intensity-modulated radiation therapy

Cited by 14 publications

References 23 publications

CD133+ cells contribute to radioresistance via altered regulation of DNA repair genes in human lung cancer cells

CD133+ cells contribute to radioresistance via altered regulation of DNA repair genes in human lung cancer cells

The Role of the Core Non-Homologous End Joining Factors in Carcinogenesis and Cancer

Roles of glucose transporter-1 and the phosphatidylinositol 3-kinase/protein kinase B pathway in cancer radioresistance (Review)

Contact Info

Product

Resources

About