title: Majority of differentially expressed genes are down-regulated during malignant transformation in a four-stage model.
abstract: The transformation of normal cells to malignant, metastatic tumor cells is a multistep process caused by the sequential acquirement of genetic changes. To identify these changes, we compared the transcriptomes and levels and distribution of proteins in a four-stage cell model of isogenically matched normal, immortalized, transformed, and metastatic human cells, using deep transcriptome sequencing and immunofluorescence microscopy. The data show that ∼6% (n = 1,357) of the human protein-coding genes are differentially expressed across the stages in the model. Interestingly, the majority of these genes are down-regulated, linking malignant transformation to dedifferentiation. The up-regulated genes are mainly components that control cellular proliferation, whereas the down-regulated genes consist of proteins exposed on or secreted from the cell surface. As many of the identified gene products control basic cellular functions that are defective in cancers, the data provide candidates for follow-up studies to investigate their functional roles in tumor formation. When we further compared the expression levels of four of the identified proteins in clinical cancer cohorts, similar differences were observed between benign and cancer cells, as in the cell model. This shows that this comprehensive demonstration of the molecular changes underlying malignant transformation is a relevant model to study the process of tumor formation.
authors.affiliation: Science for Life Laboratory, Royal Institute of Technology (KTH), SE-17121 Solna, Sweden.
authors.forename: Frida
authors.initials: F
authors.lastname: Danielsson
authors.forename: Marie
authors.initials: M
authors.lastname: Skogs
authors.forename: Mikael
authors.initials: M
authors.lastname: Huss
authors.forename: Elton
authors.initials: E
authors.lastname: Rexhepaj
authors.forename: Gillian
authors.initials: G
authors.lastname: O'Hurley
authors.forename: Daniel
authors.initials: D
authors.lastname: Klevebring
authors.forename: Fredrik
authors.initials: F
authors.lastname: Pontén
authors.forename: Annica K B
authors.initials: AK
authors.lastname: Gad
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlén
authors.forename: Emma
authors.initials: E
authors.lastname: Lundberg
mesh_terms: D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D011905:Genes, ras / Q000502:physiology; D056726:Genetic Association Studies; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D025341:Principal Component Analysis; D011506:Proteins / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism
chemical_list: D000952:Antigens, Polyomavirus Transforming; D011506:Proteins; C509186:TERT protein, human; D019098:Telomerase