Study on the Mechanism of Cell Cycle Checkpoint Kinase 2 (CHEK2) Gene Dysfunction in Chemotherapeutic Drug Resistance of Triple Negative Breast Cancer Cells

Luo, Li; Gao, Wei; Wang, Jinghui; Wang, Dingxue; Peng, Xiaobo; Jia, Zhongzhi; Jiang, Ye; Li, Gongzhuo; Tang, Dongdong; Wang, Yajie

doi:10.12659/msm.907256

Cited by 18 publications

(12 citation statements)

References 26 publications

(19 reference statements)

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“…However, exposure to IR may contribute to interruption of the G1/S transition, resulting in S-phase arrest. In theory, G1/S arrest would give cells with radiation exposure more time to perform DNA damage repair [207][208][209] . Previous studies have indicated that p53, a famous transcription factor, regulates the cell cycle 210,211 , especially by monitoring G1 and G2/M checkpoints 195 .…”

Section: Activation Of Cell Cycle Checkpointsmentioning

confidence: 99%

DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer

Huang

Zhou

2020

Sig Transduct Target Ther

603

457

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Radiotherapy is one of the most common countermeasures for treating a wide range of tumors. However, the radioresistance of cancer cells is still a major limitation for radiotherapy applications. Efforts are continuously ongoing to explore sensitizing targets and develop radiosensitizers for improving the outcomes of radiotherapy. DNA double-strand breaks are the most lethal lesions induced by ionizing radiation and can trigger a series of cellular DNA damage responses (DDRs), including those helping cells recover from radiation injuries, such as the activation of DNA damage sensing and early transduction pathways, cell cycle arrest, and DNA repair. Obviously, these protective DDRs confer tumor radioresistance. Targeting DDR signaling pathways has become an attractive strategy for overcoming tumor radioresistance, and some important advances and breakthroughs have already been achieved in recent years. On the basis of comprehensively reviewing the DDR signal pathways, we provide an update on the novel and promising druggable targets emerging from DDR pathways that can be exploited for radiosensitization. We further discuss recent advances identified from preclinical studies, current clinical trials, and clinical application of chemical inhibitors targeting key DDR proteins, including DNA-PKcs (DNA-dependent protein kinase, catalytic subunit), ATM/ATR (ataxia-telangiectasia mutated and Rad3-related), the MRN (MRE11-RAD50-NBS1) complex, the PARP (poly[ADP-ribose] polymerase) family, MDC1, Wee1, LIG4 (ligase IV), CDK1, BRCA1 (BRCA1 C terminal), CHK1, and HIF-1 (hypoxia-inducible factor-1). Challenges for ionizing radiation-induced signal transduction and targeted therapy are also discussed based on recent achievements in the biological field of radiotherapy.

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Section: Activation Of Cell Cycle Checkpointsmentioning

confidence: 99%

DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer

Huang

Zhou

2020

Sig Transduct Target Ther

603

457

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“…With improvements in molecular biology and genomics, the importance of analysis of breast cancer tumors at the molecular level for gene and protein expression, prior to administering chemotherapy, has become increasingly recognized [ 11 , 12 ]. The cell surface receptor tyrosine kinase, c-Met, belongs to the MET gene family, and its ligand is hepatocyte growth factor (HGF), both of which play important roles in cell proliferation, cell differentiation, tissue regeneration, cell survival, and tumor invasion [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Increased Expression of c-Met is Associated with Chemotherapy-Resistant Breast Cancer and Poor Clinical Outcome

et al. 2018

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BackgroundThe relevance of c-Met expression as a prognostic or predictive clinical indicator in chemotherapy-resistant breast cancer remains unknown. The aims of this study were to investigate the expression of c-Met in breast cancer tissues and its association with expression of type II topoisomerase (TOPO II), including in patients who received neoadjuvant chemotherapy (NAC), and to investigate chemotherapy resistance in vitro in breast cancer cell lines.Material/MethodsTissue samples from 255 patients with breast cancer, with matched adjacent normal breast tissue, were used in tissue microarrays (TMAs). c-Met protein expression levels were determined using immunohistochemistry. Forty-five cases of breast cancer treated with NAC were studied to investigate the association between c-Met and TOPO II expression and clinical outcome. Chemotherapy resistance was evaluated in vitro in the MCF-7 and MDA-MB-231 breast cancer cell lines.ResultsExpression of c-Met protein was increased in breast cancer tissue compared with normal breast tissue. In breast cancer tissue samples, increased c-Met expression was significantly associated with increased Ki-67 expression, tumor size, tumor stage, and TOPO II expression, and with reduced overall survival (OS) rates. Increased c-Met expression and reduced TOPO II expression were associated with chemotherapy resistance. In breast cancer cell lines, knockdown of c-Met expression induced TOPO II expression and increased tumor cell sensitivity to chemotherapy.ConclusionsThe findings of this study support a role for c-Met as a clinical prognostic marker and for c-Met and TOPO II as predictive markers for response to chemotherapy in patients with breast cancer.

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“…2c), as observed by their original manuscripts [32,35,39,44,64]. However, this cellular process is highly complex, involving several components that could regulate it positively or negatively, and it has been widely studied as it is crucial for resistant subpopulation rising, not only to TMX but also to other drugs [72][73][74][75].…”

Section: Discussionmentioning

confidence: 96%

Molecular markers associated with the outcome of tamoxifen treatment in estrogen receptor-positive breast cancer patients: scoping review and in silico analysis

Berto

Santos

et al. 2021

Discov Onc

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Tamoxifen (TMX) is used as adjuvant therapy for estrogen receptor-positive (ER+) breast cancer cases due to its affinity and inhibitory effects. However, about 30% of cases show drug resistance, resulting in recurrence and metastasis, the leading causes of death. A literature review can help to elucidate the main cellular processes involved in TMX resistance. A scoping review was performed to find clinical studies investigating the association of expression of molecular markers profiles with long-term outcomes in ER+ patients treated with TMX. In silico analysis was performed to assess the interrelationship among the selected markers, evaluating the joint involvement with the biological processes. Forty-five studies were selected according to the inclusion and exclusion criteria. After clustering and gene ontology analysis, 23 molecular markers were significantly associated, forming three clusters of strong correlation with cell cycle regulation, signal transduction of proliferative stimuli, and hormone response involved in morphogenesis and differentiation of mammary gland. Also, it was found that overexpression of markers in selected clusters is a significant indicator of poor overall survival. The proposed review offered a better understanding of independent data from the literature, revealing an integrative network of markers involved in cellular processes that could modulate the response of TMX. Analysis of these mechanisms and their molecular components could improve the effectiveness of TMX.

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Study on the Mechanism of Cell Cycle Checkpoint Kinase 2 (CHEK2) Gene Dysfunction in Chemotherapeutic Drug Resistance of Triple Negative Breast Cancer Cells

Cited by 18 publications

References 26 publications

DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer

DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer

Increased Expression of c-Met is Associated with Chemotherapy-Resistant Breast Cancer and Poor Clinical Outcome

Molecular markers associated with the outcome of tamoxifen treatment in estrogen receptor-positive breast cancer patients: scoping review and in silico analysis

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