scholarly journals Genome-wide DNA methylome analysis reveals novel epigenetically dysregulated non-coding RNAs in human breast cancer

2014 ◽  
Author(s):  
Yongsheng Li ◽  
Yunpeng Zhang ◽  
Shengli Li ◽  
Jianping Lu ◽  
Juan Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Target Genes ◽  
Cpg Islands ◽  
Aberrant Methylation ◽  
Breast Cancers ◽  
Human Breast ◽  
Protein Coding ◽  
Methylome Analysis ◽  
Non Coding Rnas

The development of human breast cancer is driven by changes in the genetic and epigenetic landscape of the cell. Despite growing appreciation of the importance of epigenetics in breast cancers, our knowledge of epigenetic alterations of non-coding RNAs (ncRNAs) in breast cancers remains limited. Here, we explored the epigenetic patterns of ncRNAs in breast cancers via a sequencing-based comparative methylome analysis, mainly focusing on two most popular ncRNA biotypes, long non-coding RNAs (lncRNAs) and miRNAs. Besides global hypomethylation and extensive CpG islands (CGIs) hypermethylation, we observed widely aberrant methylation in the promoters of ncRNAs, which was higher than that of protein-coding genes. Specifically, intergenic ncRNAs were observed to contribute a large slice of the aberrantly methylated ncRNA promoters. Moreover, we summarized five patterns of ncRNA promoter aberrant methylation in the context of genomic CGIs, where aberrant methylation occurred not only on the CGIs, but also flanking regions and CGI sparse promoters. Integration with transcriptional datasets, we found that the ncRNA promoter methylation events were associated with transcriptional changes. Furthermore, a panel of ncRNAs were identified as biomarkers that were able to discriminate between disease phenotypes (AUCs>0.90). Finally, the potential functions for aberrantly methylated ncRNAs were predicted based on similar patterns, adjacency and/or target genes, highlighting that ncRNAs and coding genes coordinately mediated pathways dysregulation in the development and progression of breast cancers. This study presents the aberrant methylation patterns of ncRNAs, which will be a highly valuable resource for investigations at understanding epigenetic regulation of breast cancers.

scholarly journals Genome-wide DNA methylome analysis reveals epigenetically dysregulated non-coding RNAs in human breast cancer

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Yongsheng Li ◽  
Yunpeng Zhang ◽  
Shengli Li ◽  
Jianping Lu ◽  
Juan Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Human Breast ◽  
Dna Methylome ◽  
Genome Wide ◽  
Methylome Analysis ◽  
Non Coding Rnas

scholarly journals Extracellular Calcium-Sensing Receptor Expression and Its Potential Role in Regulating Parathyroid Hormone-Related Peptide Secretion in Human Breast Cancer Cell Lines*

Endocrinology ◽  
2000 ◽  
Vol 141 (12) ◽  
pp. 4357-4364 ◽  
Author(s):  
Jennifer L. Sanders ◽  
Naibedya Chattopadhyay ◽  
Olga Kifor ◽  
Toru Yamaguchi ◽  
Robert R. Butters ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Human Breast Cancer ◽  
Cancer Cell Lines ◽  
Human Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Human Breast

Abstract Metastasis of breast cancer to bone occurs with advanced disease and produces substantial morbidity. Secretion of PTH-related peptide (PTHrP) from breast cancer cells is thought to play a key role in osteolytic metastases and is increased by transforming growth factor-β (TGFβ), which is released from resorbed bone. Elevated extracellular calcium (Cao2+) also stimulates PTHrP secretion from various normal and malignant cells, an action that could potentially be mediated by the Cao2+-sensing receptor (CaR) originally cloned from the parathyroid gland. Indeed, we previously showed that both normal breast ductal epithelial cells and primary breast cancers express the CaR. In this study we investigated whether the MCF-7 and MDA-MB-231 human breast cancer cell lines express the CaR and whether CaR agonists modulate PTHrP secretion. Northern blot analysis and RT-PCR revealed bona fide CaR transcripts, and immunocytochemistry and Western analysis with a specific anti-CaR antiserum demonstrated CaR protein expression in both breast cancer cell lines. Furthermore, elevated Cao2+ and the polycationic CaR agonists, neomycin and spermine, stimulated PTHrP secretion dose dependently, with maximal, 2.1- to 2.3-fold stimulation. In addition, pretreatment of MDA-MB-231 cells overnight with TGFβ1 (0.2, 1, or 5 ng/ml) augmented both basal and high Cao2+-stimulated PTHrP secretion. Thus, in PTHrP-secreting breast cancers metastatic to bone, the CaR could potentially participate in a vicious cycle in which PTHrP-induced bone resorption raises the levels of Cao2+ and TGFβ within the bony microenvironment, which then act in concert to evoke further PTHrP release and worsening osteolysis.

scholarly journals Characterization of organoid cultured human breast cancer

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Nadine Goldhammer ◽  
Jiyoung Kim ◽  
Vera Timmermans-Wielenga ◽  
Ole William Petersen
Keyword(s):  
Breast Cancer ◽  
Primary Breast Cancer ◽  
Human Breast Cancer ◽  
Breast Cancers ◽  
Basal Cells ◽  
Human Breast ◽  
Contemporary Culture ◽  
Mucin 1 ◽  
Organoid Cultures ◽  
Primary Human Breast

AbstractOrganoid cultures are increasingly used to model human cancers experimentally with a view to tailoring personalized medicine and predicting drug responses. Breast cancer is no exception, but in particular, primary breast cancer poses some inherent difficulties due to the frequent presence of residual non-malignant cells in the biopsies. We originally developed an assay for the distinction between malignant and non-malignant structures in primary breast cancer organoid cultures (Petersen et al., Proc Natl Acad Sci (USA) 89(19):9064–8, 1992). Here, we apply this assay to assess the frequency of normal-like organoids in primary breast carcinoma cultures and the cellular composition as a consequence of passaging. We find that in consecutively collected samples of primary human breast cancers, residual non-malignant tissues were observed histologically in five out of ten biopsies. Based on relevant morphogenesis and correct polarization as recorded by expression in luminal epithelial cells of mucin 1 (Muc1), occludin, and keratin 19 (K19) and expression in basal cells of integrin β4, p63, and K14, non-malignant organoids were present in all primary human breast cancer-derived cultures. Furthermore, passaging in a contemporary culture medium was in favor of the selective expansion of basal-like cells. We conclude that organoid cultures of human breast cancers are most representative of the tissue origin in primary culture.

Immunohistochemical Study of Ten Cases of Argyrophilic Carcinoma (Carcinoid) of the Breast

1988 ◽  
Vol 74 (3) ◽  
pp. 295-302 ◽  
Author(s):  
Salvatore Andreola ◽  
Emanuela Di Re ◽  
Mirella Merson ◽  
Lorenza Maggiulli ◽  
Patrizia De Palma
Keyword(s):  
Breast Cancer ◽  
Natural History ◽  
Human Breast Cancer ◽  
Immunohistochemical Study ◽  
Secretory Activity ◽  
Controversial Issue ◽  
Breast Cancers ◽  
Human Breast ◽  
History Of

The significance of argyrophilia in human breast cancer is still a controversial issue. We tested immunohistochemically 10 cases of argyrophilic carcinomas of the breast and found evidence of immunoreactivity with neuroendocrine markers: chromogranin, NSE, gastrin, insulin and bombesin. Argyrophilia was demonstrated in breast cancers of the usual types and was found to be related to the secretory activity of neoplastic cells. Unfortunately, no adequate follow-up data are available to clarify the natural history of argyrophilic breast cancer. A clinical treatment different from that of conventional breast cancer is not at present justified.

scholarly journals Long non-coding RNAs as prognostic markers in human breast cancer

Oncotarget ◽  
2016 ◽  
Vol 7 (15) ◽  
pp. 20584-20596 ◽  
Author(s):  
Hairong Liu ◽  
Juan Li ◽  
Pratirodh Koirala ◽  
Xianfeng Ding ◽  
Binghai Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Prognostic Markers ◽  
Human Breast ◽  
Non Coding Rnas

A novel therapeutic strategy for ER-negative human breast cancers, targeting AP-1 activity

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14129-14129
Author(s):  
K. Sakaguchi ◽  
H. Nakajima ◽  
I. Fujiwara ◽  
N. Mizuta ◽  
J. Magae
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Human Breast Cancer ◽  
Human Breast Cancer Cell ◽  
Breast Cancers ◽  
Human Breast ◽  
Er Positive

14129 Background: While agents targeting estrogen receptors are the most effective in adjuvant therapy for human breast cancers expressing estrogen receptor(ER), breast cancers lacking ER are clinically serious, because they are highly malignant and exhibit resistance to the usual anti-cancer drugs, including estrogen receptor-antagonists and DNA breaking agents. Although a transcription factor, AP-1, is known to be related to tumor malignancy including metastasis, invasion and drug-resistance, it remains to be elucidated how AP-1 plays in development and expression of malignant characters of human breast cancers. Methods and Results: Here, we used MX-1, a human breast cancer cell line lacking ER and several ER positive cell lines, to clarify the roles of AP-1 and the therapeutic efficacy of ascochlorin, a newly developed prenylphenol antibiotic on ER-negative breast cancer. We found that MX-1 exhibited higher AP-1 activity and expressed higher levels of c-Jun, c-Fos and Fra-1 when compared with conventional ER-positive human breast cancer cell lines. Consistent with this study in vitro, histological study on human breast cancer tissues suggests that ER-negative cancers express high Fra-1 protein, and that paclitaxel- sensitive cancers express low Fra-1 protein. The ascochlorin, which inhibits AP-1 through the Erk signaling pathway, suppressed the AP-1 activity of MX-1 cells, and selectively killed MX-1 cells, partly due to induction of apoptosis. Moreover, administration of ascochlorin elongated life span of mice intraperitoneally implanted with murine mammary carcinoma cells. Conclusions: Our results suggest that AP-1 is an effective clinical target molecule for the treatment of ER-negative human breast cancer, and that ascochlorin is promising therapeutic agent for these refractory breast cancers. No significant financial relationships to disclose.

scholarly journals Primate-specific oestrogen-responsive long non-coding RNAs regulate proliferation and viability of human breast cancer cells

Open Biology ◽  
2016 ◽  
Vol 6 (12) ◽  
pp. 150262 ◽  
Author(s):  
Chin-Yo Lin ◽  
Erica L. Kleinbrink ◽  
Fabien Dachet ◽  
Juan Cai ◽  
Donghong Ju ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Oestrogen Receptor ◽  
Breast Cancer Cells ◽  
Signalling Pathways ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs) are transcripts of a recently discovered class of genes which do not code for proteins. LncRNA genes are approximately as numerous as protein-coding genes in the human genome. However, comparatively little remains known about lncRNA functions. We globally interrogated changes in the lncRNA transcriptome of oestrogen receptor positive human breast cancer cells following treatment with oestrogen, and identified 127 oestrogen-responsive lncRNAs. Consistent with the emerging evidence that most human lncRNA genes lack homologues outside of primates, our evolutionary analysis revealed primate-specific lncRNAs downstream of oestrogen signalling. We demonstrate, using multiple functional assays to probe gain- and loss-of-function phenotypes in two oestrogen receptor positive human breast cancer cell lines, that two primate-specific oestrogen-responsive lncRNAs identified in this study (the oestrogen-repressed lncRNA BC041455, which reduces cell viability, and the oestrogen-induced lncRNA CR593775, which increases cell viability) exert previously unrecognized functions in cell proliferation and growth factor signalling pathways. The results suggest that oestrogen-responsive lncRNAs are capable of altering the proliferation and viability of human breast cancer cells. No effects on cellular phenotypes were associated with control transfections. As heretofore unappreciated components of key signalling pathways in cancers, including the MAP kinase pathway, lncRNAs hence represent a novel mechanism of action for oestrogen effects on cellular proliferation and viability phenotypes. This finding warrants further investigation in basic and translational studies of breast and potentially other types of cancers, has broad relevance to lncRNAs in other nuclear hormone receptor pathways, and should facilitate exploiting and targeting these cell viability modulating lncRNAs in post-genomic therapeutics.

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