scholarly journals Induced aneuploidy disrupts MCF10A acini formation and CCND1 expression

2019 ◽  
Author(s):  
Marcel Waschow ◽  
Qi Wang ◽  
Paul Saary ◽  
Corinna Klein ◽  
Sabine Aschenbrenner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Expression Profiling ◽  
Promoter Region ◽  
3D Model ◽  
Cell Layer ◽  
Outer Cell ◽  
Mitotic Instability ◽  
Mcf10a Cells ◽  
Outer Cell Layer ◽  
The Impact

ABSTRACTAbnormal karyotypes, namely aneuploidy, can be detected in nearly all cancer entities at different grades. The impact of these altering mutations on epigenetic regulation, especially on promoter-enhancer interactions are not well understood. Here, we applied a 3D model of MCF10A cells in a high-content screen to measure induced aneuploidy by RNA interference of 82 mitotic genes associated with aneuploidy and breast cancer. Perturbation of ESPL1 and TOP2A expression led to increased mitotic instability and subsequent aneuploidy and polylobed nuclei. During acinus formation these polylobed cells disrupted proper acinus rotation inhibiting the development of a hollow lumen and a polarized outer cell layer. Further, gene expression profiling identified upregulated CCND1 among other breast cancer related genes. We show that acquisition of aneuploidy affects the morphogenesis of MCF10A acini and expression of cancer relevant genes. By conducting 4C chromosome capturing experiments we linked the alteration of interactions of the promoter region to CCND1 upregulation.

Embryonic development of the heart

Development ◽  
1969 ◽  
Vol 22 (3) ◽  
pp. 333-348
Author(s):  
Francis J. Manasek
Keyword(s):  
Cell Layer ◽  
Embryonic Heart ◽  
Outer Cell ◽  
Chick Embryos ◽  
Myocardial Wall ◽  
Undifferentiated Cells ◽  
Epicardial Layer ◽  
Outer Cell Layer ◽  
Heart Wall

The mature heart may be thought of as consisting of three layers, endocardium, myocardium, and an outer investing tissue called the epicardium. During early formation of the tubular heart of chick embryos, at about the 8-somite stage, two tissue layers become clearly discernible with the light microscope: the endocardium and the developing myocardial wall. The outer epicardial layer does not appear until later in development. It is generally accepted that embryonic heart wall or ‘epimyocardium’ is composed of muscle and undifferentiated cells. As its name implies, the epimyocardium is thought to give rise to myocardium and epicardium. Kurkiewicz (1909) suggested that the epicardium was not an epimyocardial derivative but rather is formed from cells originating in the sinus venosus region, which migrate over the surface of the heart. Nevertheless, it has become generally accepted that the outer cell layer of the embryonic heart wall differentiates in situ to give rise to the definitive visceral epicardium (Patten, 1953).

The multiple functions of the proepicardial/epicardial cell lineage in heart development

2018 ◽  
Author(s):  
Robert Dettman ◽  
Juan Antonio Guadix ◽  
Elena Cano ◽  
Rita Carmona ◽  
Ramón Muñoz-Chápuli
Keyword(s):  
Heart Development ◽  
Epithelial Mesenchymal Transition ◽  
Cardiac Development ◽  
Cell Layer ◽  
Cell Lineage ◽  
Outer Cell ◽  
Mesenchymal Transition ◽  
Myocardial Development ◽  
Epicardial Cell ◽  
Outer Cell Layer

The epicardium is the outer cell layer of the vertebrate heart. In recent years, both the embryonic and adult epicardium have revealed unsuspected peculiarities and functions, which are essential for cardiac development. In this chapter we review the current literature on the epicardium, and describe its evolutionary origin, the mechanisms leading to the induction of its extracardiac progenitor tissue, the proepicardium, and the way in which the proepicardium is transferred to the heart to form the epicardium. We also describe the epicardial epithelial–mesenchymal transition from which mesenchymal cells originate, and the developmental fate of these cells, which contribute to the vascular, interstitial, valvular, and adipose tissue. Finally, we review the molecular interactions established between the epicardium and the myocardium, which are key for myocardial development and can also play a role in cardiac homeostasis. This chapter highlights how the epicardium has become a major protagonist in cardiac biology.

The nervous system of the neotropical millipede Gymnostreptus olivaceus Schubart, 1944 (Spirostreptida, Spirostreptidae) shows an additional cell layer

2015 ◽  
Vol 65 (2) ◽  
pp. 133-150 ◽  
Author(s):  
Annelise Francisco ◽  
Roberta C.F. Nocelli ◽  
Carmem S. Fontanetti
Keyword(s):  
Nervous System ◽  
Cell Layer ◽  
Cortical Layer ◽  
Morphological Description ◽  
Outer Cell ◽  
Olfactory Glomeruli ◽  
Additional Cell ◽  
The Central Nervous System ◽  
Inner Region ◽  
Outer Cell Layer

This study presents a morphological description of the central nervous system of the neotropical millipede Gymnostreptus olivaceus and the first report of an outer cell layer surrounding the nervous system in Diplopoda. The nervous system of this species consists of a brain formed by the fusion of proto-, deuto- and tritocerebrum, as well as a ventral nerve cord with metamerically arranged ganglia that extends through the entire length of the animal’s body. The optic lobes, mushroom bodies and olfactory glomeruli of this species were located and described. As has been reported for other millipedes, the nervous system of G. olivaceus comprises a cortical layer in which three types of neurons could be identified and an inner region of neuropil, both of which are wrapped and protected by a perineurium and a neural lamella. However, more externally to the neural lamella, there is a discontinuous and irregular outer cell sheath layer containing distinctive cells whose function appears to be linked to the nutrition and protection of neurons.

Gene expression profiling and clinical relevance unravel the role hypoxia and immune signaling genes and pathways in breast cancer

2020 ◽  
Vol 1 ◽  
Author(s):  
Mohammad Azhar Kamal ◽  
Mohiuddin Khan Warsi ◽  
Afnan Alnajeebi ◽  
Haytham A Ali ◽  
Nawal Helmi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Gene Expression Profiling ◽  
Signaling Pathways ◽  
Expression Profiling ◽  
Gene List ◽  
Molecular Signatures ◽  
Biological Processes ◽  
Immune Signaling ◽  
The Impact

Hypoxia most often occurs in cancer and the occurrence of hypoxia helps the cells in adapting different responses than the normal such as the activation of of those signaling pathways which regulate proliferation, angiogenesis, and cell death. There are large number of genes which are known to be associated with diverse biological processes and their control and coordination and in different cancers, the hypoxia-response differs. In this study our goal is to understand the impact of alteration in expression of hypoxia and immune systems related genes and its survival in breast cancer and analyzed the hallmarks of molecular signatures. For this purpose we have collected the hypoxia-associated genes based on the literature related with diverse biological processes and functions. For all these genes, we have studied the survival analysis, breast cancer gene expression profiling, and relevant hypoxic genes alterations. Based on our study, we conclude that there are 17 critical pathways and 40 genes from hypoxic gene list appear to play the major roles in case of breast cancer and overall we observe that immune signaling pathways and its components are highly altered in case of breast cancer. Among the top raked hallmarks of molecular signatures are apoptosis, hypoxia, DNA repair, E2F targets, MYC targets, androgen and estrogen response, and TNFa signaling.

The haplotype of three polymorphisms in the SATB1 promoter-region and impact on survival in breast cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 584-584
Author(s):  
Martin Leonhard Heubner ◽  
Rainer Kimmig ◽  
Winfried Siffert ◽  
Frey Ulrich
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Promoter Region ◽  
Promoter Activity ◽  
Hek293 Cells ◽  
Nucleotide Polymorphisms ◽  
Breast Cancer Patients ◽  
Regulatory Effects ◽  
The Impact

584 Background: Special AT-rich sequence binding protein 1 (SATB1) has regulatory effects on gene expression and appears to play an important role in tumor progression. We screened the promoter region of the SATB1 gene for polymorphisms, evaluated the corresponding haplotypes regarding alterations in promoter activity in vitro and analyzed the impact of these haplotypes on the clinical course of breast cancer patients. Methods: 241 caucasian breast cancer patients who had been treated were enrolled in this retrospective analysis. The median follow up time was 93 months (4-155 months). PCR products from DNA of 10 healthy unrelated volunteers were analyzed to identify new polymorphisms within the promoter region. Genotyping was conducted using restriction length polymorphism and pyrosequencing. PCR constructs with the respective alleles from the four most frequent haplotypes were cloned into the vector pGEM-Teasy (Promega Corporation, Madison, WI, USA) and then transferred into the luc2-containing reporter vector pGl 4.10 Vector (Promega) for transfection of HEK293 cells. The pGl 4.73 Vector (Promega), containing hRluc, was used for norming the transfection rates. Results: Sequencing the region -3807bp to -2828 upstream from ATG of ten healthy blood donors, we found three single nucleotide polymorphisms SNPs consisting of base exchanges, -3600T>C, -3363A>G and -2984C>T.The SATB1 -3600T/-3363A/-2984C haplotype had a lower promoter activity than all other constructs in vitro and showed a significant association with the nodal status (p=0.049). Kaplan-Meier survival analysis revealed a significantly better survival for homozygous SATB1 -3600T/-3363A/-2984C haplotype carriers compared with heterozygous or the other haplotypes (p=0.033). Conclusions: The SATB1 -3600T/-3363A/-2984C haplotype is associated with lower promoter activity and appears to impact upon survival in breast cancer patients.

scholarly journals GENE EXPRESSION PROFILING AND EXPANDED IMMUNOHISTOCHEMISTRY TESTS TO GUIDE SELECTION OF CHEMOTHERAPY REGIMENS IN BREAST CANCER MANAGEMENT: A SYSTEMATIC REVIEW

2017 ◽  
Vol 33 (1) ◽  
pp. 32-45 ◽  
Author(s):  
Alison Scope ◽  
Munira Essat ◽  
Abdullah Pandor ◽  
Rachid Rafia ◽  
Sue E. Ward ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Systematic Review ◽  
Gene Expression Profiling ◽  
Early Breast Cancer ◽  
Expression Profiling ◽  
Clinical Effectiveness ◽  
Clinicopathological Parameters ◽  
Cancer Management ◽  
The Impact

Objectives:The aim of this report was to assess the clinical effectiveness of two Gene expression profiling (GEP) and two expanded immunohistochemistry (IHC) tests compared with current prognostic tools in guiding the use of adjuvant chemotherapy in patients with early breast cancer.Methods:A systematic review of the evidence on clinical effectiveness of OncotypeDX, IHC4, MammaPrint, and Mammostrat, compared with current clinical practice using clinicopathological parameters, in women with early breast cancer was conducted. Ten databases were searched to include citations to May 2016.Results:Searches identified 7,064 citations, of which forty-one citations satisfied the criteria for the review. A narrative synthesis was performed. Evidence for OncotypeDX demonstrated the impact of the test on decision making and there was some support for OncotypeDX predicting chemotherapy benefit. There were relatively lower levels of evidence for the other three tests included in the analysis. MammaPrint, Mammostrat, and IHC4 tests were limited to a small number of studies. Limitations in relation to study design were identified for all tests.Conclusions:The evidence base for OncotypeDX is considered to be the most robust. Methodological weaknesses relating to heterogeneity of patient cohorts and issues arising from the retrospective nature of the evidence were identified. Further evidence is required for all of the tests using prospective randomized controlled trial data.

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