The AGMK1-9T7 cell model of neoplasia: Evolution of DNA copy-number aberrations and miRNA expression during transition from normal to metastatic cancer cells.

Autor: Lewis AM Jr; Laboratory of DNA Viruses, Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United States of America., Thomas R; Department of Molecular Biomedical Sciences, College of Veterinary Medicine, and Center for Comparative Medicine and Translational Research, Raleigh, NC, United States of America., Breen M; Department of Molecular Biomedical Sciences, College of Veterinary Medicine, and Center for Comparative Medicine and Translational Research, Raleigh, NC, United States of America., Peden K; Laboratory of DNA Viruses, Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United States of America., Teferedegne B; Laboratory of DNA Viruses, Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United States of America., Foseh G; Laboratory of DNA Viruses, Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United States of America., Motsinger-Reif A; Bioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh NC, United States of America., Rotroff D; Bioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh NC, United States of America., Lewis G; TCL and M Associates, Leesburg, VA, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2022 Oct 24; Vol. 17 (10), pp. e0275394. Date of Electronic Publication: 2022 Oct 24 (Print Publication: 2022).
DOI: 10.1371/journal.pone.0275394
Abstrakt: To study neoplasia in tissue culture, cell lines representing the evolution of normal cells to tumor cells are needed. To produce such cells, we developed the AGMK1-9T7 cell line, established cell banks at 10-passage intervals, and characterized their biological properties. Here we examine the evolution of chromosomal DNA copy-number aberrations and miRNA expression in this cell line from passage 1 to the acquisition of a tumorigenic phenotype at passage 40. We demonstrated the use of a human microarray platform for DNA copy-number profiling of AGMK1-9T7 cells using knowledge of synteny to 'recode' data from human chromosome coordinates to those of the African green monkey. This approach revealed the accumulation of DNA copy-number gains and losses in AGMK1-9T7 cells from passage 3 to passage 40, which spans the period in which neoplastic transformation occurred. These alterations occurred in the sequences of genes regulating DNA copy-number imbalance of several genes that regulate endothelial cell angiogenesis, survival, migration, and proliferation. Regarding miRNA expression, 195 miRNAs were up- or down-regulated at passage 1 at levels that appear to be biologically relevant (i.e., log2 fold change >2.0 (q<0.05)). At passage 10, the number of up/down-regulated miRNAs fell to 63; this number increased to 93 at passage 40. Principal-component analysis grouped these miRNAs into 3 clusters; miRNAs in sub-clusters of these groups could be correlated with initiation, promotion, and progression, stages that have been described for neoplastic development. Thirty-four of the AGMK1-9T7 miRNAs have been associated with these stages in human cancer. Based on these data, we propose that the evolution of AGMK1-9T7 cells represents a detailed model of neoplasia in vitro.
Competing Interests: DMR has stock and other ownership interests in Clarified Precision Medicine, LLC., has served in a consultant and advisory role for Pharmazam LLC and Interpares Biomedicine, has received research funding from Novo Nordisk Inc., and has intellectual property related to the detection of liver cancer. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Databáze: MEDLINE
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