Change search
ReferencesLink to record
Permanent link

Direct link
The Global Protein Expression Pattern in Human Cell Lines
KTH, School of Biotechnology (BIO), Proteomics.ORCID iD: 0000-0003-0198-7137
KTH, School of Biotechnology (BIO), Proteomics.
Show others and affiliations
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Human cancer cell lines grown in vitro are frequently used to decipher basic cell biological phenomena but also to specifically study different forms of cancer. Here we present the first large-scale study of protein expression patterns in cell lines using an antibody-based proteomics approach. We analyzed the expression pattern of 5436 proteins in 45 different cell lines using hierarchical clustering, principal component analysis and two-group comparisons for the identification of differentially expressed proteins. The results show that protein profiles of cell lines, as determined using immunohistochemistry, allow for a hierarchical clustering that overall reflects tumor tissues of origin. Hematological cell lines appear to retain their protein profiles to a higher degree than cell lines established from solid tumors, resulting in a clustering that well reflects progenitor cell types. The discrepancy may reflect different levels of in vitro induced alterations in adherent and suspension grown cell lines, respectively. In addition, multiple myeloma cells and cells of myeloid origin were found to share a protein profile, relative the protein profile of lymphoid leukemia and lymphoma cells, possibly reflecting their common dependency of bone marrow microenvironment.


National Category
Other Industrial Biotechnology
URN: urn:nbn:se:kth:diva-31510OAI: diva2:404448
Available from: 2011-03-17 Created: 2011-03-17 Last updated: 2011-03-17Bibliographically approved
In thesis
1. Mapping the human proteome using bioinformatic methods
Open this publication in new window or tab >>Mapping the human proteome using bioinformatic methods
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The fundamental goal of proteomics is to gain an understanding of the expression and function of the proteome on the level of individual proteins, on the level of defined cell types and on the level of the entire organism. In this thesis, the human proteome is explored using membrane protein topology prediction methods to define the human membrane proteome and by global protein expression profiling, which relies on a complex study of the location and expression levels of proteins in tissues and cells.

A whole-proteome analysis was performed based on the predicted protein-coding genes of humans using a selection of membrane protein topology prediction methods. The study used a majority decision-based method, which estimated that approximately 26% of the human genes encode for a membrane protein. The prediction results are displayed in a visualization tool to facilitate the selection of antigens to be used for antibody generation.

Global protein expression profiles in a large number of cells and tissues in the human body were analyzed for more than 4000 protein targets, based on data from the antibody-based immunohistochemistry and immunofluorescence methods within the framework of the Human Protein Atlas project. The results revealed few cell-type specific proteins and a high fraction of human proteins expressed in most cells, suggesting that cell and tissue specificity is attained by a fine-tuned regulation of protein levels. The expression profiles were also used to analyze the relationship between 45 cell lines by hierarchical clustering and principal component analysis. The global protein expression patterns overall reflected the tumor origin of the cells, and also allowed for identification of proteins of importance for distinguishing different categories of cell lines, as defined by phenotype of progenitor cell. In addition, the protein distribution in 16 subcellular compartments in three of the human cell lines was mapped. A large fraction of proteins were localized in two or more compartments and, in line with previous results, a majority of proteins were detected in all three cell lines.

Finally, mass spectrometry-based protein expression levels were compared to RNA-seq-based transcript expression levels in three cell lines. Highly ubiquitous mRNA expression was found and the changes of expression levels between the cell lines showed high correlations between proteins and transcripts. Large general differences in abundance of proteins from various functional classes were observed. A comparison between categories based on expression levels revealed that, in general, genes with varying expression levels between the cell lines or only expressed in one cell line were highly enriched for cell-surface proteins.

These studies show a path for a systematic analysis to characterize the proteome in human cells, tissues and organs.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology., 2011. 66 p.
Trita-BIO-Report, ISSN 1654-2312 ; 2011:4
proteome, transcriptome, bioinformatics, membrane protein prediction, subcellular localization, protein expression level, cell line, immunohistochemistry, immunofluorescence
National Category
Bioinformatics and Systems Biology
Research subject
SRA - Molecular Bioscience
urn:nbn:se:kth:diva-31477 (URN)978-91-7415-886-1 (ISBN)
Public defence
2011-04-08, F3, Lindstedtsvägen 26, KTH, Stockholm, 14:41 (English)
The Human Protein Atlas project
Knut and Alice Wallenberg Foundation
QC 20110317Available from: 2011-03-17 Created: 2011-03-16 Last updated: 2011-03-17Bibliographically approved

Open Access in DiVA

No full text

Search in DiVA

By author/editor
Fagerberg, LinnGry, MarcusUhlén, Mathias
By organisation
Other Industrial Biotechnology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 41 hits
ReferencesLink to record
Permanent link

Direct link