Highly adaptable triple-negative breast cancer cells as a functional model for testing anticancer agents
| Autor: | Ryan D. Milligan, Amanda M. Cady, Anthony Lucci, Balraj Singh, Anna Shamsnia, Simran Madan, Milan R. Raythatha |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Epithelial-Mesenchymal Transition
Blotting Western Cancer Treatment Alpha-Ketoglutarate-Dependent Dioxygenase FTO lcsh:Medicine Antineoplastic Agents Triple Negative Breast Neoplasms Disease Biology Real-Time Polymerase Chain Reaction Bioinformatics Metastasis Mice Downregulation and upregulation Basic Cancer Research Breast Tumors Breast Cancer Biomarkers Tumor Tumor Cells Cultured Medicine and Health Sciences Animals Humans Obesity RNA Messenger Epithelial–mesenchymal transition lcsh:Science Chemotherapeutic Agents Triple-negative breast cancer Comparative Genomic Hybridization Multidisciplinary Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling lcsh:R Proteins Cancers and Neoplasms Adaptation Physiological Gene Expression Regulation Neoplastic Gene expression profiling Oncology Drug Resistance Neoplasm Cell culture Cancer cell Carcinogens Cancer research Female Oncology Agents lcsh:Q Research Article |
| Zdroj: | PLoS ONE, Vol 9, Iss 10, p e109487 (2014) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | A major obstacle in developing effective therapies against solid tumors stems from an inability to adequately model the rare subpopulation of panresistant cancer cells that may often drive the disease. We describe a strategy for optimally modeling highly abnormal and highly adaptable human triple-negative breast cancer cells, and evaluating therapies for their ability to eradicate such cells. To overcome the shortcomings often associated with cell culture models, we incorporated several features in our model including a selection of highly adaptable cancer cells based on their ability to survive a metabolic challenge. We have previously shown that metabolically adaptable cancer cells efficiently metastasize to multiple organs in nude mice. Here we show that the cancer cells modeled in our system feature an embryo-like gene expression and amplification of the fat mass and obesity associated gene FTO. We also provide evidence of upregulation of ZEB1 and downregulation of GRHL2 indicating increased epithelial to mesenchymal transition in metabolically adaptable cancer cells. Our results obtained with a variety of anticancer agents support the validity of the model of realistic panresistance and suggest that it could be used for developing anticancer agents that would overcome panresistance. |
| Databáze: | OpenAIRE |
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