Red and green indicate an increase and decrease of gene expression, respectively. There are 63 genes in this category. Last, Fig. Genes with the highest node degree were considered as hub genes of the network. Network 1 and Network 2 Fig. Network 1 contains 71 significantly enriched genes and 20 predicted, while Network 2 consists of 64 identified DEGs and 20 predicted genes. Nodes in blue are selected genes, nodes in green are GeneMania predicted genes, nodes in red represent hub genes.
Network 3 and Network 4 Fig. Meanwhile, Network 6 with genes from the CSC-DLD1 cell line consisted of 64 genes from the cell interaction category and 20 predicted genes identified by network construction analysis. The fold change ratios of selected genes are displayed in Fig. Overall, a correlation between the microarray and qPCR results was observed. Validation of microarray gene expression data by qPCR using selected genes. Each bar represents the mean and standard deviations of three independently performed experiments for RT-qPCR. Three-dimensional 3D cell culture systems are introduced in cancer research as gene expression and cellular signaling patterns as well as phenotypic characteristics of 3D cultured cells tend to mimic profiles of in vivo tissues more precisely compared to monolayer cell cultures [ 15 ].
Considering this, 3D culturing of reprogrammed normal colon and carcinoma cells may provide an appropriate model to investigate the maintenance of cancer stemness. In this study, we compared genome-wide expression profiles of reprogrammed human colon normal CRL and carcinoma DLD1 cells grown in more physiologically relevant three-dimensional 3D versus traditional monolayer 2D cell cultures.
Moreover, these data demonstrated that CRL — colon normal and DLD1 — colon cancer cell lines share many common pathways after being reprogrammed and cultured under 3D conditions. We identified several groups of DEGs in both reprogrammed cell lines that could be associated to the cancer cell resistance to a particular type of cancer treatment.
In accord to our observation, changes in an integrin expression under 3D cell culture conditions resulted in an altered proliferation and apoptosis, and therefore increased cellular resistance to radiation and chemotherapy [ 9 , 24 ]. Gangadhara et al.
Related to this, the regulation of the genes coding Ras superfamily was also altered. Previous studies have pointed out small GTPases as targets of the MAPK signaling pathway, in promoting cancer transformation processes [ 26 ]. Interestingly, these changes were observed in both cell lines suggesting the application of normal cell lines in cancer remodeling research.
We also discovered an additional family of deregulated genes belonging to the cell interaction functional category. Most of these genes were down-regulated. Whereas other studies demonstrated that the microtubules are involved in regulation of p53 activity by its translocation to the nucleus in a complex with heat shock protein 90 HSP90 , which provides stability for the p53 protein [ 27 , 28 , 29 ].
Microarray results revealed a down-regulation of genes encoding HSP90 in both cell lines as well, fortifying the supposition that the changes in p53 regulation are influenced by 3D cell culture conditions. These changes in regulation of the p53 signaling pathway might be as well related to the maintenance of the stemness state under the specific microenvironment. This probably leads to the maintenance of the stem-like phenotype, together increasing the precedent for the changes in cell death regulation and proliferation promotion as discussed above.
- Genetic characterization of commonly used glioma cell lines in the rat animal model system.
- Selecting the appropriate cell line.
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Furthermore, a decrease in the expression level of a group of human leukocyte antigen HLA encoding genes was observed in both reprogrammed cell lines. These findings are consistent with the Pick et al. Since HLA genes are responsible for major histocompatibility complex MHC protein expression, this could also serve positively in modulation of cancer cell mechanisms involved in evading immune response. Carter et al. In addition, despite that the majority of stemness-related genes were down-regulated, a few that are important for proliferation and self-renewal were up-regulated.
This might be one of the factors promoting the stemness status in our experimental system. Additionally, the expression of SIAH1 decreased in both cell lines. Also, the results above are consistent with the role of p53 in up-regulating the BAX gene which is involved in pmediated apoptosis [ 35 ]. The study conducted by Lee et al. Interestingly, this change of expression was common for both reprogrammed cell lines — colon normal and carcinoma. Since changes in gene regulation belonging to the mentioned pathways suggest promotion of proliferation and inhibition of apoptosis, it might explain tendency of iPSC-CRL to display properties typical for cancer cells after differentiating from the pluripotent state under 3D cell culture conditions.
Our study indicated that reprogrammed human colon normal and colon carcinoma cell lines share a common profile of gene expression under more physiologically relevant 3D spheroid versus 2D monolayer cell culture conditions.
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The result of the KEGG pathway enrichment analysis demonstrated that downstream signaling events of the p53 pathway might lead to an inhibition of cell cycle arrest, cellular senescence, and apoptosis. Finally, our findings demonstrate that pathways important for cancer transformation and tumor metastatic activity are altered during the transition from 2D to 3D culture conditions both in normal and cancer stem-like cells. Prospective identification of tumorigenic breast cancer cells.
Proc Natl Acad Sci. Stem cells, cancer, and cancer stem cells. Decreased mitochondrial priming determines chemoresistance of colon cancer stem cells. Cell Death Differ. Cancer stem cells - perspectives on current status and future directions: AACR workshop on cancer stem cells. Cancer Res. Cancer stem cells - old concepts, new insights. Cancer stem cell: fundamental experimental pathological concepts and updates. Exp Mol Pathol. Yoshida GJ, Saya H. Therapeutic strategies targeting cancer stem cells. Cancer Sci. Induction of cells with cancer stem cell properties from nontumorigenic human mammary epithelial cells by defined reprogramming factors.
Associations of chemo- and radio-resistant phenotypes with the gap junction, adhesion and extracellular matrix in a three-dimensional culture model of soft sarcoma. J Exp Clin Cancer Res. Breast cancer stem cells, cytokine networks, and the tumor microenvironment. J Clin Invest.
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Defined factors induce reprogramming of gastrointestinal cancer cells. A cancer reprogramming method using MicroRNAs as a novel therapeutic approach against colon cancer. Ann Surg Oncol. Importantly, EBV can transform latently infected primary cells from healthy individuals into cancerous ones, thereby causing important human cancers such as B-cell neoplasms e.
Burkitt's lymphoma and Post-transplant lymphomas , certain forms of T-cell lymphoma, and some epithelial tumours e. Understanding viral latency, what triggers viral reactivation and the mechanism of transformation of normal host cells into malignant cells are critical for the development of strategies for the prevention and control of this intriguing virus and related cancers.
In this book, expert EBV virologists comprehensively review this important subject from a genetic, biochemical, immunological, and cell biological perspective. This book is essential reading for all EBV virologists as well as clinical and basic scientists working on oncogenic viruses. Books Site Journal Backlist Gateway. Issues Mol. How to Order. Library recommendation email pdf. Download flyer.
References and Recommended Reading
Latent Epstein-Barr Virus Infections. EBV latent infection of B-lymphocytes is necessary for virus persistence, subsequent replication in epithelial cells, and release of infectious virus into saliva. This introduction highlights key aspects of what has been learned over the past 45 years about the role of EBV Latent infection associated gene expression in maintaining EBV episomes in dividing cells and in increasing cell growth and survival. We expect that a clear view of the current picture and access to more detailed references can be useful for applying new experimental approaches.
The ensuing chapters are intended to fulfill those missions. Epstein-Barr Virus Leader Protein. The functions of these cofactors implicate EBNA-LP as a potential modulator of apoptosis, cell cycle processes, and transcriptional pathways. EBNA1 is the latent origin binding protein of Epstein-Barr virus and the only viral protein needed for the replication and stable persistence of EBV episomes.
The gene products that were highlighted after intersecting the lists generated by the two methods of analysis were scrutinized against changes in gene expression reported in the literature.
Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells
Tumorigenesis involves three major steps: the accumulation of genetic alterations, uncontrolled growth, and selected survival of transformed cells. The discussion of the results focuses attention on genes whose primary function is in pathways involved in glioma proliferation, infiltration, and neovascularization. A comparative microarray analysis of differentially expressed genes for four of the commonly used rat tumor cell lines is presented here. Due to the variances between the cell lines and results from analyses in humans, caution must be observed in interpreting as well as in the translation of information learned from animal models to its application in human trials.
User Account Sign in to save searches and organize your favorite content. Not registered? Sign up My Content 1 Recently viewed 1 Genetic characterizati Search Close Advanced Search Help. Genetic characterization of commonly used glioma cell lines in the rat animal model system. Zita A. Full access. Download PDF. Rhoton Anatomy Links.
Related Gene Expression in Normal and Transformed Cells
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