Expression patterns of the <i>ATM</i> gene in mammary tissues and their associations with breast cancer survival

Ye, Chuanzhong; Cai, Qiuyin; Dai, Qi; Shu, Xiao‐Ou; Shin, Aesun; Gao, Yu‐Tang; Wang, Zheng

doi:10.1002/cncr.22592

Cited by 39 publications

(29 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, low ATM expression has been associated with an increased risk of death in colorectal and breast cancers. 12,14 Again, these inconsistencies may be the results of many factors, including different cancer types, different histology and tumor characteristics, and accuracy in measuring mRNA expression. In addition, all of the literature on the prognostic value of ATM, DNA-PKcs, and Ku80 discussed above were based on gene expression in tumor tissues.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Prognostic significance of ataxia‐telangiectasia mutated, DNA‐dependent protein kinase catalytic subunit, and Ku heterodimeric regulatory complex 86‐kD subunit expression in patients with nonsmall cell lung cancer

Xing

Vaporciyan

et al. 2008

Cancer

View full text Add to dashboard Cite

BACKGROUND.The double‐strand break (DSB) repair capacity has been implicated in the survival of patients in several cancer types. However, little is known about the prognostic importance of the key DSB repair genes—ataxia‐telangiectasia mutated (ATM), DNA‐dependent protein kinase catalytic subunit (DNA‐PKcs), and the Ku heterodimeric regulatory complex 86‐kD subunit (Ku80)—in nonsmall cell lung cancer (NSCLC). To address this issue, the authors determined the messenger RNA (mRNA) expression of these genes in patients NSCLC and assessed their prognostic relevance.METHODS.mRNA expression levels of ATM, DNA‐PKcs, and Ku80 were measured in tumor and adjacent normal tissues from 140 patients with NSCLC by using quantitative real‐time polymerase chain reaction analysis. Then, a Cox proportional hazards regression model and Kaplan‐Meier plots were used to evaluate the association between the tumor:normal (T/N) expression ratios of the 3 genes and the overall survival rate and duration in patients with NSCLC.RESULTS.mRNA expression of ATM and DNA‐PKcs, but not of Ku80, was significantly higher in tumor tissues than in adjacent normal tissues (P = .003 and P < .001, respectively). The high T/N expression ratios of ATM and DNA‐PKcs were associated significantly with a 1.82‐fold increased risk of death (95% confidence interval, 1.05–2.70) and a 2.13‐fold increased risk of death (95% confidence interval, 1.21–3.76), respectively. However, no significant association with risk was observed for Ku80. Kaplan‐Meier analyses revealed that patients with high T/N expression ratios of ATM or DNA‐PKcs had notably shorter median survival than patients with low ratios.CONCLUSIONS.The current findings suggested that the T/N expression ratios of ATM and DNA‐PKcs may be useful for identifying NSCLC patients with a poor prognosis who may benefit from more aggressive therapy. Cancer 2008. ©2008 American Cancer Society.

show abstract

Section: Discussionmentioning

confidence: 99%

“…12,13 Accordingly, the prognostic value of ATM expression in colorectal and breast cancer has been investigated. 12,14 However, to our knowledge, its significance in lung cancer has not been studied.…”

mentioning

confidence: 99%

Prognostic significance of ataxia‐telangiectasia mutated, DNA‐dependent protein kinase catalytic subunit, and Ku heterodimeric regulatory complex 86‐kD subunit expression in patients with nonsmall cell lung cancer

Xing

Vaporciyan

et al. 2008

Cancer

View full text Add to dashboard Cite

show abstract

“…genów dla cykliny E i D1 [22], a białko E2F1 w nadekspresji indukuje zarówno zależną od P53, jak i niezależną apoptozę i reguluje promotor BRCA1 i RB u ludzi [23]. Wyniki wielu badań in vivo i in vitro sugerują, że niska ekspresja ATM w komórkach raka piersi koreluje z występowaniem mutacji DNA, ze zwiększoną angiogenezą, a zatem progresywnym fenotypem nowotworu [24]. Konserwatywne białko jądrowe wiążące P53 -TP53BP1 -jest głównym przekaźnikiem sygnałów o uszkodzeniu DNA do P53 i innych białek supresorowych nowotworów [25].…”

Section: Dyskusjaunclassified

Analysis of expression of selected genes coding transcriptional activators in ductal breast cancer cells in vitro treated with paclitaxel

Ziaja‐Sołtys¹,

Rzymowska²

2011

View full text Add to dashboard Cite

A Ai im m o of f t th he e s st tu ud dy y: : The aim of our studies was to assess the influence of paclitaxel on the expression of selected activating transcriptional factors in ductal breast cancer primary cells using the microarray technique. M Ma at te er ri ia al l a an nd d m me et th ho od ds s: : The cells were treated with 60 ng/ml and 300 ng/ml doses of paclitaxel. Administered dose concentrations corresponded to those applied in breast cancer mono-and polytherapy and also covered the number of chemotherapy cycles. The control breast cancer cells in vitro were not treated with a cytostatic drug. R Re es su ul lt ts s: : Sixteen among 21 analysed genes indicated statistically significant increased expression in the cells incubated with 60 ng/ml of paclitaxel: 15 genes in the 1.8-3.3 fold range (p < 0.05), but ETS1 gene expression level increased 4.7-fold in comparison to the control cells. The higher dose of 300 ng/ml of paclitaxel caused a cytotoxic effect in the cells and a statistically non-significant decrease in expression of all studied genes. C Co on nc cl lu us si io on ns s: : In summary it may be stated that a 60 ng/ml dose of paclitaxel caused increased expression of analysed genes coding transcriptional activating factors that enhance the studied taxane's mechanism of action. Thus we can suppose that these changes in gene expression values may constitute prognostic and predictive factors in ductal breast cancer therapy. The obtained results encourage us to carry out further studies on the functions and relations between genes and their products. K Ke ey y w wo or rd ds s: : breast cancer, transcriptional activators, paclitaxel, microarrays.Contemporary Oncology (2011) vol. 15; 2 (69-73)

show abstract

“…The phosphorylation of DNA damage response (DDR) proteins as well as ATM was demonstrated as a major mechanism of tumor evolution in various types of cancer [6,7]. Moreover, aberrant expression of ATM has been demonstrated in gastric, adenocortical, prostate, colorectal, and breast cancers [8][9][10][11][12]. Inefficiency of cells to repair DNA damage as a consequence of defects in DDR encoding genes was described as a possible reason for inducing brain tumor development [13].…”

Section: Introductionmentioning

confidence: 98%

Linking ATM Promoter Methylation to Cell Cycle Protein Expression in Brain Tumor Patients: Cellular Molecular Triangle Correlation in ATM Territory

et al. 2014

View full text Add to dashboard Cite

Ataxia telangiectasia mutated (ATM) is a key gene in DNA double-strand break (DSB), and therefore, most of its disabling genetic alterations play an important initiative role in many types of cancer. However, the exact role of ATM gene and its epigenetic alterations, especially promoter methylation in different grades of brain tumors, remains elusive. The current study was conducted to query possible correlations among methylation statue of ATM gene, ATM/ retinoblastoma (RB) protein expression, D1853N ATM polymorphism, telomere length (TL), and clinicopathological characteristics of various types of brain tumors. Isolated DNA from 30 fresh tissues was extracted from different types of brain tumors and two brain tissues from deceased normal healthy individuals. DNAs were treated with bisulfate sodium using DNA modification kit (Qiagen). Methylation-specific polymerase chain reaction (MSP-PCR) was implicated to determine the methylation status of treated DNA templates confirmed by promoter sequencing. Besides, the ATM and RB protein levels were determined by immunofluorescence (IF) assay using monoclonal mouse antihuman against ATM, P53, and RB proteins. To achieve an interactive correlation, the methylation data were statistically analyzed by considering TL and D1853N ATM polymorphism. More than 73% of the brain tumors were methylated in ATM gene promoter. There was strong correlation between ATM promoter methylation and its protein expression (p < 0.001). As a triangle, meaningful correlation was also found between methylated ATM promoter and ATM protein expression with D1853N ATM polymorphism (p = 0.01). ATM protein expression was not in line with RB protein expression while it was found to be significantly correlated with ATM promoter methylation (p = 0.01). There was significant correlation between TL neither with ATM promoter methylation nor with ATM protein expression nor with D1853N polymorphism. However, TL has shown strong correlation with patient's age and tumor grade (p = 0.01). Given the important role of cell cycle checkpoint proteins as well as RB and ATM in TL and cancer evolution, further assessment is warranted to shed more light on the pathway linking the telomere instability to tumor progression. High ATM methylation rate in brain tumor patients could open a new avenue toward early screening and cancer therapy.

show abstract

Expression patterns of the ATM gene in mammary tissues and their associations with breast cancer survival

Cited by 39 publications

References 31 publications

Prognostic significance of ataxia‐telangiectasia mutated, DNA‐dependent protein kinase catalytic subunit, and Ku heterodimeric regulatory complex 86‐kD subunit expression in patients with nonsmall cell lung cancer

Prognostic significance of ataxia‐telangiectasia mutated, DNA‐dependent protein kinase catalytic subunit, and Ku heterodimeric regulatory complex 86‐kD subunit expression in patients with nonsmall cell lung cancer

Analysis of expression of selected genes coding transcriptional activators in ductal breast cancer cells in vitro treated with paclitaxel

Linking ATM Promoter Methylation to Cell Cycle Protein Expression in Brain Tumor Patients: Cellular Molecular Triangle Correlation in ATM Territory

Contact Info

Product

Resources

About