scholarly journals A novel histone H4 variant H4G regulates rDNA transcription in breast cancer

2019 ◽  
Vol 47 (16) ◽  
pp. 8399-8409 ◽  
Author(s):  
Mengping Long ◽  
Xulun Sun ◽  
Wenjin Shi ◽  
An Yanru ◽  
Sophia T C Leung ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle Progression ◽  
Gene Expression Regulation ◽  
Alpha Helix ◽  
Cell Types ◽  
Tumor Stage ◽  
Histone Variants ◽  
Histone H4 ◽  
Breast Cancer Patients ◽  
Rdna Transcription

AbstractHistone variants, present in various cell types and tissues, are known to exhibit different functions. For example, histone H3.3 and H2A.Z are both involved in gene expression regulation, whereas H2A.X is a specific variant that responds to DNA double-strand breaks. In this study, we characterized H4G, a novel hominidae-specific histone H4 variant. We found that H4G is expressed in a variety of human cell lines and exhibit tumor-stage dependent overexpression in tissues from breast cancer patients. We found that H4G localized primarily to the nucleoli of the cell nucleus. This localization was controlled by the interaction of the alpha-helix 3 of the histone fold motif with a histone chaperone, nucleophosmin 1. In addition, we found that modulating H4G expression affects rRNA expression levels, protein synthesis rates and cell-cycle progression. Our data suggest that H4G expression alters nucleolar chromatin in a way that enhances rDNA transcription in breast cancer tissues.

scholarly journals A novel histone H4 variant regulates rDNA transcription in breast cancer

2018 ◽  
Author(s):  
Mengping Long ◽  
Xulun Sun ◽  
Wenjin Shi ◽  
Yanru An ◽  
Tsz Chui Sophia Leung ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle Progression ◽  
Gene Expression Regulation ◽  
Alpha Helix ◽  
Histone Variants ◽  
Micrococcal Nuclease ◽  
Histone H4 ◽  
Breast Cancer Patients ◽  
Rdna Transcription

AbstractHistone variants, present in various cell types and tissues, are known to exhibit different functions. For example, histone H3.3 and H2A.Z are both involved in gene expression regulation, whereas H2A.X is a specific variant that responds to DNA double-strand breaks. In this study, we characterized H4G, a novel hominidae-specific histone H4 variant. H4G expression was found in a variety of cell lines and was particularly overexpressed in the tissues of breast cancer patients. H4G was found to localize primarily to the nucleoli of the cell nucleus. This localization was controlled by the interaction of the alpha helix 3 of the histone fold motif with the histone chaperone, nucleophosphomin 1. In addition, we found that H4G nucleolar localization increased rRNA levels, protein synthesis rates, and cell cycle progression. Furthermore, micrococcal nuclease digestion of H4G-containing nucleosomes reconstitutedin vitroindicated that H4G destabilizes the nucleosome, which may serve to alter nucleolar chromatin in a way that enhances rDNA transcription in breast cancer tissues.

Associations between polymorphisms at microRNA-binding sites in TYMS and breast cancer risk among Chinese women

2020 ◽  
Author(s):  
Meng Wang ◽  
Jia Yao ◽  
Yi Zheng ◽  
Yuyao Yao ◽  
Shuqian Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Chinese Women ◽  
Microarray Dataset ◽  
Tumor Stage ◽  
Recessive Model ◽  
Breast Cancer Patients ◽  
Chinese Han ◽  
Expression Levels

Abstract Studies have suggested that thymidylate (TYMS) polymorphisms are associated with breast cancer. However, inconsistent results were obtained and data from Asian populations are largely lacking. In this study, the relationships between two common TYMS polymorphisms (rs2790 and rs1059394) and the breast cancer risk were evaluated. We also studied the TYMS expression between tumor and para-carcinoma tissues, and the association between TYMS levels and prognosis of breast cancer. This hospital-based study included 434 patients and 450 cancer-free individuals. Genotying was performed using Sequenom Mass-ARRAY. The microarray dataset GSE115144 was downloaded to compare the differences in TYMS expression between tumor and para-carcinoma tissues. The microarray dataset GSE20685 was used to analysis the metastasis free survival (MFS) and overall survival (OS) of patients. The rs2790 polymorphism was related to a higher risk of breast cancer (recessive model: OR=1.50, 95%CI=1.02-2.21, P=0.038) and the C allele of rs1059394 was overrepresented in patients with tumor stage III-IV (heterozygote model: OR=0.60, 95%CI=0.39-0.94, P=0.025; dominant model: OR=0.59, 95%CI=0.39-0.89, P=0.013). The tumor tissues had a higher TYMS expression levels and patients with higher TYMS expression levels had worse OS. Overall, TYMS polymorphism may increase susceptibility to breast cancer in Chinese Han women and TYMS expression levels may be a predictive factor for breast cancer patients.

Comparison of CA 15-3 and CEA in diagnosis and monitoring of breast cancer

1989 ◽  
Vol 4 (4) ◽  
pp. 207-214 ◽  
Author(s):  
F. Safi ◽  
I. Kohler ◽  
E. Röttinger ◽  
P. Suhr ◽  
H. G. Beger
Keyword(s):  
Breast Cancer ◽  
Serum Levels ◽  
Tumor Stage ◽  
Breast Cancer Patients ◽  
Curative Surgery ◽  
Benign Diseases ◽  
Breast Cancer Metastases ◽  
Normal Limits ◽  
Cancer Metastases ◽  
Tumor Associated Antigen

In order to assess the utility of the tumor-associated antigen CA15-3 in the diagnosis of breast cancer, this new tumor marker was measured pre-operatively in 1342 patients. This group comprised 509 patients with malignant disease (134 with breast cancer and 375 with other malignancies not involving the breast) and 833 patients with benign surgical diseases (95 patients with fibroadenoma of the breast, 738 with other benign diseases). The results were compared with those for carcino-embryonic antigen (CEA) in the diagnosis of breast cancer. CA15-3 was above the normal limits of 25 U/ml in 31% of the patients with breast cancer, in 22% of patients with other malignancies, and in 9% of patients with benign diseases. CEA was elevated in 26% of patients with breast cancer (> 3ng/ml). CA15-3 levels were above 50 U/ml in 13% of the breast cancer patients, in 6%) of patients with other malignancies, and in 0.2% of the patients with benign diseases. There was a good correlation between CA 15-3 level and tumor stage in breast cancer. CA 15-3 serum levels were over 50 U/ml in respectively 0%, 2%, 13%, and 73% of the patients with stages I, II, III, and IV. CA 15-3 and CEA were also determined in 671 patients who had received initial curative surgery of breast cancer, and who regularly attended our follow-up clinic. CA15-3 was found to be more sensitive than CEA in detecting recurrences of breast cancer. In the post-care period, carcinoma recurred in 205 patients. Of these 73% had CA15-3 concentrations above 25 U/ml, whereas only 50% had CEA values above 3 ng/ml (p< 0.0001). Although neither CA15-3 nor CEA are sensitive enough for the screening and diagnosis of early breast cancer, CA 15-3 is superior to CEA in the detection of breast cancer metastases.

scholarly journals Expression and Clinical Significance of Origin Recognition Complex Family in Breast Cancer

2021 ◽  
Author(s):  
shaohua chen ◽  
Ziyao Jin ◽  
Linfeng Xin ◽  
Lv Lv ◽  
Xuemei Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Origin Recognition Complex ◽  
Diagnostic Value ◽  
Breast Cancer Patients ◽  
Cycle Progression ◽  
Poor Prognostic Factor ◽  
Node Metastasis ◽  
Cancer Tissues

Abstract BackgroundThe aim of this study is to investigate the potential clinical and prognostic value, role and driving molecular mechanisms of the origin recognition complex family in breast cancer.Resultsata from Oncomine, TCGA, GEO and ULCAN showed that ORC1L and ORC6L were highly expressed in breast cancer tissues, while the expression of ORC5L was inconsistent and there was no significant difference in the expression of ORC2L, ORC3L and ORC4L. High expression of ORC1L and ORC6L were mainly Her2 overexpressed subtype, and their expression were negatively correlated with patient age and positively correlated with tumor size, but not with lymph node metastasis, distant metastasis, or tumor stage. Expression of ORC5L was also negatively correlated with age and positively correlated with lymph node metastasis, but not with breast cancer molecular subtype and tumor size. Expression of ORC1L and ORC5L had high diagnostic value, and ORC6L had the highest diagnostic value in breast cancer. ORC6L was an independent poor prognostic factor for overall survival of breast cancer patients. It was involved in cell cycle progression, cell senescence, epigenetic regulation and other biological functions, and may regulate signaling pathways such as NF-KB, TP53 and WNT in breast cancer. We also found that the expression of ORC6L was related to the increased infiltration of Th1/2 cell and Treg cell, and decreased infiltration of Mast cell and NK cell.ConclusionsORC1L and ORC6L are highly expressed in breast cancer tissues, of which ORC6L has high diagnostic value and is an independent poor prognostic factor for overall survival of breast cancer patients. ORC6L may be involved in the occurrence and progression of breast cancer by regulating cell cycle progression, promoting the activation of cancer signaling pathways, and influencing tumor immune cells infiltration.

scholarly journals Histopathologic Characteristics of Invasive and Non-invasive Ductal Tumors have Relationship with Different Phenotypes of ER / PR Receptors in Breast Cancer Patients

2021 ◽  
Vol 6 (3) ◽  
pp. 181-185
Author(s):  
Rahim Golmohammadi ◽  
Mohammad Reza Mohajeri ◽  
Alireza Mosavi Jarrahi ◽  
Ali Reza Moslem ◽  
Akbar Pejhan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Hormone Receptors ◽  
Ductal Carcinoma ◽  
Tumor Grade ◽  
Tumor Stage ◽  
Tumor Type ◽  
Breast Cancer Patients ◽  
Non Invasive ◽  
Significant Difference

Objective: Contradictory reports have been published regarding the expression levels of the hormone receptors of estrogen and progesterone (ER / PR) and theirclinical importance in diagnosis of breast cancer. The aim of this study was to evaluate the relationship between pathological features of invasive and non-invasive ductal tumors by different ER / PR phenotypes. Methods: This descriptive-analytical study was performed on 74 specimens of breast cancer referred to Isfahan Hospitals for diagnosis between 2015 - 2018. After fixation of the specimens in formalin, tissue passage, cross section and H / E staining, the specimens were divided into two groups: non- invasive and Invasive ductal Carcinoma. After removing of mask, expression of different ER / PR phenotypes was performed using primary monoclonal antibody and immunohistochemically methods. Results: From 74 malignant specimens, 61 (82.4%) were in the category of invasive ductal tumors and 13 cases (17.6%) were in the category of non-invasive ductal tumors. Out of 73 patients with positive ER or PR phenotype 47 samples (63.5%) had ER + / PR +phenotypes, 6 samples had (8.1%) ER+ / PR –phenotype, 20 samples (27%) had ER- / PR + phenotype and only one sample (1.4%) had the ER- / PR- phenotype and was in the category of invasive ductal tumors. There was not detected ER- / PR- phenotype expression in non-invasive ductal tumor. Further analysis showed that there were not significant difference between ER / PR phenotype and tumor stage (p =0.36) or with tumor Grade (P=0.38), high age of menopause or post menopause (P> 0.05). Conclusion: Our data shows that expression of ER- / PR- phenotype only was detected in invasive ductal tumor. It is thought that the tumor type maybe affects the expression of different types of ER / PR hormone receptor phenotypes in breast cancer patients.

scholarly journals HuR Reduces Radiation-Induced DNA Damage by Enhancing Expression of ARID1A

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2014 ◽  
Author(s):  
Daniel Andrade ◽  
Meghna Mehta ◽  
James Griffith ◽  
Sangphil Oh ◽  
Joshua Corbin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Rna Binding ◽  
Breast Cancer Patients ◽  
Dna Double Strand Breaks ◽  
End Joining ◽  
Wide Range ◽  
Non Homologous End Joining

Tumor suppressor ARID1A, a subunit of the chromatin remodeling complex SWI/SNF, regulates cell cycle progression, interacts with the tumor suppressor TP53, and prevents genomic instability. In addition, ARID1A has been shown to foster resistance to cancer therapy. By promoting non-homologous end joining (NHEJ), ARID1A enhances DNA repair. Consequently, ARID1A has been proposed as a promising therapeutic target to sensitize cancer cells to chemotherapy and radiation. Here, we report that ARID1A is regulated by human antigen R (HuR), an RNA-binding protein that is highly expressed in a wide range of cancers and enables resistance to chemotherapy and radiation. Our results indicate that HuR binds ARID1A mRNA, thereby increasing its stability in breast cancer cells. We further find that ARID1A expression suppresses the accumulation of DNA double-strand breaks (DSBs) caused by radiation and can rescue the loss of radioresistance triggered by HuR inhibition, suggesting that ARID1A plays an important role in HuR-driven resistance to radiation. Taken together, our work shows that HuR and ARID1A form an important regulatory axis in radiation resistance that can be targeted to improve radiotherapy in breast cancer patients.

Impact of mammographic screening in staging, treatment and prognosis of breast cancer: Early assessment

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10537-10537
Author(s):  
A. Lluch ◽  
I. Chirivella ◽  
A. Insa ◽  
F. Martinez-Ruiz ◽  
A. Santaballa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Cancer Patients ◽  
Breast Conserving Surgery ◽  
Tumor Stage ◽  
Mammographic Screening ◽  
Invasive Breast Carcinoma ◽  
Breast Cancer Patients ◽  
Early Assessment ◽  
The Impact

10537 Background: The use of breast cancer mammographic screening (MS) leads to early detection and has been shown to reduce the mortality rate and to increase the proportion of breast-conserving surgery. The aim of this study is to analyze the impact of mammography in the staging, treatment and prognosis of breast carcinoma. Methods: In 1993, a population-based mammographic screening among women aged from 45 to 70 years was introduced in the community of Valencia. We examined the effects of this MS program by the comparison of two populations. The first one included all the women with screen-detected invasive breast carcinoma between 1993 and 2002 in the community of Valencia. The second one was comprised of all the women with invasive breast carcinoma, diagnosed in the same period, aged 45–70, not attending the MS and treated at H. Clinico of Valencia. Results: Between January, 1993 and December, 2002, 2313 new invasive breast cancer patients were detected by the MS program in the community of Valencia, and 1349 women aged 45–70, not attending de MS were diagnosed with invasive breast carcinoma in H.Clinico of Valencia. The median follow-up period was 45.5 months for the screen-detected breast cancer and 51.9 months for not screen-detected patients. The screen-detected tumors had smaller pathological size (pT1 tumors 70.2% vs 40.5%, p < 0.0001), were more likely to have pathologically confirmed negative nodal status (66.4% vs 52.2%, p < 0.0001) and stage I disease (55.3% vs 26.1%, p < 0.0001). Breast-conserving surgery was performed in 50.4% of patients with screen-detected tumors and in 31.9% of women who had not undergone MS (p < 0.0001). The 5-year estimated survival was 95.5% (SE 0.57) for women with screen-detected breast cancer and 85.5% (SE 1.17) for those with not screen-detected tumors (p < 0.0001). Conclusions: Our data demonstrate a better prognosis in terms of 5-year survival in screen-detected breast cancer patients that may explain why breast carcinoma mortality rates have decreased in recent decades. These patients have also been found to have smaller tumors, a more favorable tumor stage and a higher proportion of breast-conserving surgery. No significant financial relationships to disclose.

Evaluation of basal and luminal subtypes of urothelial carcinoma in African American and non-African American patients.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 305-305 ◽  
Author(s):  
Jordan Kardos ◽  
Jonathan J Melquist ◽  
David D. Chism ◽  
Woonyoung Choi ◽  
Katherine Cockerill ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
African American ◽  
Urothelial Carcinoma ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Tumor Stage ◽  
Intrinsic Subtype ◽  
Breast Cancer Patients ◽  
Muscle Invasive

305 Background: African American (AA) patients with urothelial carcinoma (UC) have been known to have a worse prognosis even when corrected for variables such as tumor stage and grade. Analysis of gene expression of several malignancies has resulted in the discovery of molecular subtypes with well-defined intrinsic biology. Recent studies in high grade (HG), muscle-invasive UC have led to the identification of two intrinsic, molecular subsets termed “luminal” and “basal” with characteristics of stages of urothelial differentiation, and that remarkably reflect the luminal and basal-like molecular subtypes of breast cancer. Patients with basal-like UC have a significantly worse overall survival. Methods: A total of 215 HG muscle-invasive UC tumors from the MDACC (n=75) and TCGA (n=140) were used to make intrinsic subtype calls using gene expression profiling (MDACC: DASL [cDNA-mediated Annealing, Selection, extension, and Ligation] and TCGA: RNA seq). Basal and luminal subtype calls were derived using previously published subtype classifiers (Damrauer et. al. PNAS, 2014 and Choi et. al. Cancer Cell, 2014). Patients were classified into AA and non-AA (white, Hispanic, or Asian) based upon self-reported race. Results: In total there were 16 and 199 tumors from AA and non-AA patients respectively. In non-AA patients, the proportion of tumors that were classified as basal and luminal were approximately equal (93 and 106 respectively), while in AA patients, there was enrichment of basal tumors (12 basal and 4 luminal) (p=0.03735, Fisher’s exact test). Conclusions: AA patients are enriched in the basal molecular subtype of UC. Similar findings have been previously documented in AA women with breast cancer. The enrichment of basal UC in AAs suggests that a biological explanation may in part underlie the poor outcomes seen in AA patients. Future studies will explore the prognostic and predictive implications of basal subtype in AA patients with UC.

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