uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Platelet-derived growth factor receptor expression and activation in choroid plexus tumors
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Show others and affiliations
2009 (English)In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 175, no 4, 1631-1637 p.Article in journal (Refereed) Published
Abstract [en]

Choroid plexus tumors are intraventricular neoplasms predominantly affecting young children. In contrast to choroid plexus papillomas, choroid plexus carcinomas progress frequently, necessitating the development of adjuvant treatment concepts. Platelet derived growth factor (PDGF) signaling has been shown to support growth in a variety of tumors. The finding of PDGF receptor expression in choroid plexus tumors prompted us to elucidate PDGF receptor activation state using a novel method, in situ proximity ligation assay, on formalin-fixed, paraffin-embedded, archival samples of 19 choroid plexus tumors. As assessed by in situ proximity ligation assay, the proportion of phosphorylated PDGF receptor alpha was low in choroid plexus papillomas and choroid plexus carcinomas, whereas phosphorylated PDGF receptor beta was found to be significantly higher in choroid plexus carcinomas. In the immortalized choroid plexus epithelial cell line Z310 expressing PDGF receptor beta, PDGF-BB exhibited a time- and dose-dependent proliferative response, which was significantly attenuated by imatinib (gleevec). In conclusion, our findings suggest that PDGF receptor beta is functionally involved in the biology of choroid plexus tumors and may represent a molecular target for therapy. In addition, this study demonstrates the feasibility and usefulness of in situ proximity ligation assay for monitoring receptor tyrosine kinase activation in formalin-fixed, paraffin-embedded, archival tissues.

Place, publisher, year, edition, pages
2009. Vol. 175, no 4, 1631-1637 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-112105DOI: 10.2353/ajpath.2009.081022ISI: 000270503100029PubMedID: 19717644OAI: oai:DiVA.org:uu-112105DiVA: diva2:284918
Available from: 2010-01-08 Created: 2010-01-08 Last updated: 2011-01-13Bibliographically approved
In thesis
1. Visualization of Protein Activity Status in situ Using Proximity Ligation Assays
Open this publication in new window or tab >>Visualization of Protein Activity Status in situ Using Proximity Ligation Assays
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In 2001 the human proteome organization (HUPO) was created with the ambition to identify and characterize all proteins encoded in the human genome according to several criteria; their expression levels in different tissues and under different conditions; the sub-cellular localization; post-translational modifications; interactions, and if possible also the relationship between their structure and function.When the knowledge of different proteins and their potential interactions increases, so does the need for methods able to unravel the nature of molecular processes in cells and organized tissues, and ultimately for clinical use in samples obtained from patients.

The in situ proximity ligation assay (in situ PLA) was developed to provide localized detection of proteins, post-translational modifications and protein-protein interactions in fixed cells and tissues. Dual recognition of the target or interacting targets is a prerequisite for the creation of a circular reporter DNA molecule, which subsequently is locally amplified for visualization of individual protein molecules in single cells. These features offer the high sensitivity and selectivity required for detection of even rare target molecules.

Herein in situ PLA was first established and then employed as a tool for detection of both interactions and post-translational modifications in cultured cells and tissue samples. In situ PLA was also adapted to high content screening (HCS) for therapeutic effects, where it was applied for cell-based drug screening of inhibitors influencing post-translational modifications. This was performed using primary cells, paving the way for evaluation of drug effects on cells from patient as a diagnostic tool in personalized medicine.

In conclusion, this thesis describes the development and applications of in situ PLA as a tool to study proteins, post-translational modifications and protein-protein interactions in genetically unmodified cells and tissues, and for clinical interactomics.


Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 44 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 609
proximity ligation, in situ, high content screening, platelet-derived growth factor receptor, rolling circle amplification, protein interactions, in situ PLA, post-translational modifications, drug screening
National Category
Cell and Molecular Biology Medical Genetics
Research subject
Molecular Medicine
urn:nbn:se:uu:diva-131934 (URN)978-91-554-7919-0 (ISBN)
Public defence
2010-12-04, Rudbecksalen, Rudbecklaboratoriet, Dag Hammarskjölds väg 20, Uppsala, 09:15 (English)
Available from: 2010-11-11 Created: 2010-10-11 Last updated: 2011-01-13Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Söderberg, Ola
By organisation
Department of Genetics and Pathology
In the same journal
American Journal of Pathology
Medical and Health Sciences

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

Altmetric score

Total: 220 hits
ReferencesLink to record
Permanent link

Direct link