| 1. |
- Asplund, Anna, et al.
(author)
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Antibodies for profiling the human proteome-The Human Protein Atlas as a resource for cancer research
- 2012
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In: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 12:13, s. 2067-2077
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Journal article (peer-reviewed)abstract
- In this review, we present an update on the progress of the Human Protein Atlas, with an emphasis on strategies for validating immunohistochemistry-based protein expression patterns and on the possibilities to extend the map of protein expression patterns for cancer research projects. The objectives underlying the Human Protein Atlas include (i) the generation of validated antibodies toward a major isoform of all proteins encoded by the human genome, (ii) creating an information database of protein expression patterns in normal human tissues, in cells, and in cancer, and (iii) utilizing generated antibodies and protein expression data as tools to identify clinically useful biomarkers. The success of such an effort is dependent on the validity of antibodies as specific binders of intended targets in applications used to map protein expression patterns. The development of strategies to support specific target binding is crucial and remains a challenge as a large fraction of proteins encoded by the human genome is poorly characterized, including the approximately one-third of all proteins lacking evidence of existence. Conceivable methods for validation include the use of paired antibodies, i.e. two independent antibodies targeting different and nonoverlapping epitopes on the same protein as well as comparative analysis of mRNA expression patterns with corresponding proteins.
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| 2. |
- Edqvist, Per-Henrik D, et al.
(author)
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Platelet-derived growth factor over-expression in retinal progenitors results in abnormal retinal vessel formation
- 2012
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:8, s. e42488-
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Journal article (peer-reviewed)abstract
- Platelet-derived growth factor (PDGF) plays an important role in development of the central nervous system, including the retina. Excessive PDGF signaling is associated with proliferative retinal disorders. We reported previously that transgenic mice in which PDGF-B was over-expressed under control of the nestin enhancer, nes/tk-PdgfB-lacZ, exhibited enhanced apoptosis in the developing corpus striatum. These animals display enlarged lateral ventricles after birth as well as behavioral aberrations as adults. Here, we report that in contrast to the relatively mild central nervous system phenotype, development of the retina is severely disturbed in nes/tk-PdgfB-lacZ mice.In transgenic retinas all nuclear layers were disorganized and photoreceptor segments failed to develop properly. Since astrocyte precursor cells did not populate the retina, retinal vascular progenitors could not form a network of vessels. With time, randomly distributed vessels resembling capillaries formed, but there were no large trunk vessels and the intraocular pressure was reduced. In addition, we observed a delayed regression of the hyaloid vasculature. The prolonged presence of this structure may contribute to the other abnormalities observed in the retina, including the defective lamination.
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| 3. |
- Pontén, Fredrik, et al.
(author)
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The Human Protein Atlas as a proteomic resource for biomarker discovery
- 2011
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 270:5, s. 428-446
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Research review (peer-reviewed)abstract
- The analysis of tissue-specific expression at both the gene and protein levels is vital for understanding human biology and disease. Antibody-based proteomics provides a strategy for the systematic generation of antibodies against all human proteins to combine with protein profiling in tissues and cells using tissue microarrays, immunohistochemistry and immunofluorescence. The Human Protein Atlas project was launched in 2003 with the aim of creating a map of protein expression patterns in normal cells, tissues and cancer. At present, 11 200 unique proteins corresponding to over 50% of all human protein encoding genes have been analysed. All protein expression data, including underlying high-resolution images, are published on the free and publically available Human Protein Atlas portal (http://www.proteinatlas.org). This database provides an important source of information for numerous biomedical research projects, including biomarker discovery efforts. Moreover, the global analysis of how our genome is expressed at the protein level has provided basic knowledge on the ubiquitous expression of a large proportion of our proteins and revealed the paucity of cell-andtissue-type-specific proteins.
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