DNA repair genes <i>PAXIP1</i> and <i>TP53BP1</i> expression is associated with breast cancer prognosis

Gregoriis, Giuliana De; Ramos, Juliene Antonio; Fernandes, Priscila Valverde; Vignal, Giselle Maria; Brianese, Rafael Canfield; Carraro, Dirce Maria; Monteiro, Alvaro N.A.; Struchiner, Cláudio J.; Suarez‐Kurtz, Guilherme; Vianna‐Jorge, Rosane; Carvalho, Marcelo A.

doi:10.1080/15384047.2017.1323590

Cited by 22 publications

(17 citation statements)

References 46 publications

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“…Thus, while we did not find statistically significant differences between the 53BP1 scores for primary TNBC and HR+ breast cancer patients, we calculated lower values for HR-versus HR+ MBC. Notably, we immunodetected 53BP1 signals in the nuclear compartment of individual CTCs, where 53BP1 acts in DSB repair, while previous work relied on tissue array or mRNA expression array data [7,9]. When we compared total cellular 53BP1 expression and nuclear accumulation of 53BP1 in cell lines by Western blot and immunofluorescence microscopy, respectively, we noticed that the discriminatory power of changes in 53BP1 signals between cells from TNBC and HR+ tumors significantly increased with microscopic imaging.…”

Section: Discussionmentioning

confidence: 94%

“…Circulating tumor cells have become the subject of intense research aiming at the detection of druggable features for personalized anticancer treatment approaches [29]. Previous studies revealed a prognostic value of 53BP1 detection in primary breast cancer [7,9,26]. Therefore, we considered whether in MBC patients, where CTCs are most prevalent, these cells are useful biopsies to monitor 53BP1 signals.…”

Section: Discussionmentioning

confidence: 99%

“…Accumulating evidence has demonstrated that loss of 53BP1 expression in breast cancer is associated with poor prognosis, particularly when focusing on TNBC patients [7,9]. Therefore we aimed at detecting 53BP1 in CTCs of MBC patients with defined HER2 and HR status to explore its potential as a biomarker.…”

Section: Detection Of 53bp1 Signals In Ctcs From Mbc Patientsmentioning

confidence: 99%

“…The DNA damage response factor 53BP1 is crucial in protecting DNA ends in BRCA1-defective cells from resection and entry into error-prone repair pathways [6][7][8]. It has been demonstrated that 53BP1 expression in breast cancer is associated with poor prognosis, particularly in TNBC frequently showing BRCA1 dysfunction [7,9].Due to the lack of predictive targets, chemotherapy was the only treatment option available for a long time. This results in an urgent clinical need for new therapies.…”

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confidence: 99%

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53BP1 Accumulation in Circulating Tumor Cells Identifies Chemotherapy-Responsive Metastatic Breast Cancer Patients

Schochter

Werner

Köstler

et al. 2020

Cancers

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Evidence suggests that the DNA end-binding protein p53-binding protein 1 (53BP1) is down-regulated in subsets of breast cancer. Circulating tumor cells (CTCs) provide accessible "biopsy material" to track cell traits and functions and their alterations during treatment. Here, we prospectively monitored the 53BP1 status in CTCs from 67 metastatic breast cancer (MBC) patients with HER2-CTCs and known hormone receptor (HR) status of the primary tumor and/or metastases before, during, and at the end of chemotherapeutic treatment with Eribulin. Nuclear 53BP1 staining and genomic integrity were evaluated by immunocytochemical and whole-genome-amplification-based polymerase chain reaction (PCR) analysis, respectively. Comparative analysis of CTCs from patients with triple-negative and HR+ tumors revealed elevated 53BP1 levels in CTCs from patients with HR+ metastases, particularly following chemotherapeutic treatment. Differences in nuclear 53BP1 signals did not correlate with genomic integrity in CTCs at baseline or with nuclear γH2AX signals in MBC cell lines, indicating that 53BP1 detected features beyond DNA damage. Kaplan-Meier analysis revealed an increasing association between nuclear 53BP1-positivity and progression-free survival (PFS) during chemotherapy until the final visit. Our data suggest that 53BP1 detection in CTCs could be a useful marker to capture dynamic changes of chemotherapeutic responsiveness in triple-negative and HR+ MBC.Cancers 2020, 12, 930 2 of 18 13.3 months after diagnosis of metastatic sites, TNBC has a particularly poor prognosis. Often patients develop a resistance to first-line chemotherapy very rapidly, resulting in a median duration of first-line palliative chemotherapy of 11.9 weeks [1].Triple-negative tumors are characterized by the lack of HR and HER2 expression, but aside from this common feature this subgroup includes very heterogeneous tumors. A mutation in BRCA1 or 2 is found in up to 20% of triple-negative metastatic patients [2]. The proteins encoded by BRCA genes are critically involved in DNA double-strand break (DSB) repair, more specifically, in the error-free pathway of homologous recombination repair (HRR) [3]. In TNBC, a high prevalence of gene mutations as well as epigenetic changes result in BRCAness, compromising safe DNA repair through HRR [2,4,5]. The DNA damage response factor 53BP1 is crucial in protecting DNA ends in BRCA1-defective cells from resection and entry into error-prone repair pathways [6][7][8]. It has been demonstrated that 53BP1 expression in breast cancer is associated with poor prognosis, particularly in TNBC frequently showing BRCA1 dysfunction [7,9].Due to the lack of predictive targets, chemotherapy was the only treatment option available for a long time. This results in an urgent clinical need for new therapies. During the last years, new drugs such as the Poly(ADP-ribose) polymerase (PARP)-inhibitors targeting HRR-defective tumors were studied in several clinical trials. Two different phase III trials (OlympiaAD and EMBRACA) showed an impro...

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Detection Of 53bp1 Signals In Ctcs From Mbc Patientsmentioning

confidence: 99%

mentioning

confidence: 99%

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53BP1 Accumulation in Circulating Tumor Cells Identifies Chemotherapy-Responsive Metastatic Breast Cancer Patients

Schochter

Werner

Köstler

et al. 2020

Cancers

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“…The human mediator of DNA damage checkpoint protein 1 (MDC1; also known as NFBD1) consists of 2,089 amino‐acid residues and has a molecular mass of approximately 220 kDa. There are two breast cancer type 1 susceptibility protein (BRCA1) carboxy‐terminal domains in the MDC1 protein, which help maintain the structural integrity of DNA, regulate cell‐cycle checkpoints through different mechanisms, and play an important role in DNA damage repair . Previous studies have shown that elevated levels of MDC1 have been detected in cervical cancer , breast cancer , and OSCC .…”

mentioning

confidence: 99%

Effect of silencing of mediator of DNA damage checkpoint protein 1 on the growth of oral squamous cell carcinoma in vitro and in vivo

Zhang

Liu

et al. 2019

European J Oral Sciences

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Effect of silencing of mediator of DNA damage checkpoint protein 1 on the growth of oral squamous cell carcinoma in vitro and in vivo. Eur J Oral Sci 2019; 127: 494-499. © 2019 Eur J Oral SciMediator of DNA damage checkpoint protein 1 (MDC1) is involved in DNA damage repair and has been linked to tumor invasion, metastasis, and prognosis. This study investigated the effects of MDC1 in oral squamous cell carcinoma (OSCC) in vitro and in vivo. RNA interference-mediated knockdown of MDC1 was performed in two OSCC cell lines (Tca-8113 and KB). Real-time PCR and western blotting were performed to determine expression of mRNA and protein, respectively, of MDC1. Cell viability was assessed using the MTT assay. Colony-formation assays were performed by staining with 0.5% crystal violet. Cell migration and invasion were detected by Transwell assays. The role of MDC1 in OSCC was examined in vivo via injection of Tca-8113 cells transfected with MDC1 small interfering (si)RNA or negative-control siRNA into a mouse xenograft model of OSCC. Our results showed that MDC1 knockdown decreased cell proliferation. Inhibition of MDC1 decreased colony formation of Tca-8113 and KB cells by 62% and 68%, respectively, and MDC1 knockdown reduced the number of migratory and invasive cells compared with the control group. Moreover, the xenograft mouse model of MDC1 knockdown showed reduced tumor growth. Our study suggests that MDC1 plays a role in tumorigenesis and might be a potential target for the treatment of patients with OSCC. Material and methods Cell cultureThe OSCC cell lines Tca-8113 and KB were obtained from the Shanghai Cell Bank of the Chinese Academy of Sciences (Shanghai, China). Both cell lines were authenticated by short tandem repeat analysis and were mycoplasma-free. Tca-8113 and KB cells were inoculated into RPMI-1640 (Gibco, Invitrogen, Paisley, UK) containing

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Generation of 3D melanoma models using an assembloid-based approach

Rodrigues,

Moreira,

Jarnalo

et al. 2024

Acta Biomaterialia

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DNA repair genes PAXIP1 and TP53BP1 expression is associated with breast cancer prognosis

Cited by 22 publications

References 46 publications

53BP1 Accumulation in Circulating Tumor Cells Identifies Chemotherapy-Responsive Metastatic Breast Cancer Patients

53BP1 Accumulation in Circulating Tumor Cells Identifies Chemotherapy-Responsive Metastatic Breast Cancer Patients

Effect of silencing of mediator of DNA damage checkpoint protein 1 on the growth of oral squamous cell carcinoma in vitro and in vivo

Generation of 3D melanoma models using an assembloid-based approach

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