Rab31 expression levels modulate tumor-relevant characteristics of breast cancer cells

Molecular Cancer

Research

Susanne Sölch¹  Manfred Schmitt¹  Viktor Magdolen¹  Bettina Grismayer¹  Sonja Schäfer¹  Bastian Seubert²  Achim Krüger²  Gustavo Baretton³  Matthias Kotzsch³  Thomas Kirchner⁴  Thomas Luther⁵ 

[1] Clinical Research Unit, Department of Obstetrics and Gynecology, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany;Institute of Experimental Oncology and Therapy Research, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany;Institute of Pathology, Dresden University of Technology, Fetscherstr. 74, 01307, Dresden, Germany;Medizinisches Labor Ostsachsen, Töpferstr. 17, 02625, Bautzen, Germany;Medizinisches Labor Ostsachsen, Töpferstr. 17, 02625, Bautzen, Germany;Institute of Pathology, Dresden University of Technology, Fetscherstr. 74, 01307, Dresden, Germany;

关键词: rab31;    Breast cancer;    GTP-binding protein;    Intracellular vesicle transport;    Proliferation;    Adhesion;    Invasion;    Tumor cell phenotype;   

DOI  :  10.1186/1476-4598-11-62

 received in 2012-04-17, accepted in 2012-08-16,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundRab proteins constitute a large family of monomeric GTP-binding proteins that regulate intracellular vesicle transport. Several Rab proteins, including rab31, have been shown to affect cancer progression and are related with prognosis in various types of cancer including breast cancer. Recently, the gene encoding rab31 was found to be overexpressed in estrogen receptor-positive breast cancer tissue. In a previous study we found a significant association of high rab31 mRNA expression with poor prognosis in node-negative breast cancer patients. In the present study, we aimed to investigate the impact of rab31 (over)-expression on important aspects of tumor progression in vitro and in vivo.MethodsBreast cancer cells displaying low (MDA-MB-231) or no (CAMA-1) endogenous rab31 expression were stably transfected with a rab31 expression plasmid. Batch-transfected cells as well as selected cell clones, expressing different levels of rab31 protein, were analyzed with regard to proliferation, cell adhesion, the invasive capacity of tumor cells, and in vivo in a xenograft tumor model. Polyclonal antibodies directed to recombinantly expressed rab31 were generated and protein expression analyzed by immunohistochemistry, Western blot analysis, and a newly developed sensitive ELISA.ResultsElevated rab31 protein levels were associated with enhanced proliferation of breast cancer cells. Interestingly, weak to moderate overexpression of rab31 in cell lines with no detectable endogenous rab31 expression was already sufficient to elicit distinct effects on cell proliferation. By contrast, increased expression of rab31 in breast cancer cells led to reduced adhesion towards several extracellular matrix proteins and decreased invasive capacity through MatrigelTM. Again, the rab31-mediated effects on cell adhesion and invasion were dose-dependent. Finally, in a xenograft mouse model, we observed a significantly impaired metastatic dissemination of rab31 overexpressing MDA-MB-231 breast cancer cells to the lung.ConclusionsOverexpression of rab31 in breast cancer cells leads to a switch from an invasive to a proliferative phenotype as indicated by an increased cell proliferation, reduced adhesion and invasion in vitro, and a reduced capacity to form lung metastases in vivo.

【 授权许可】

Unknown   
© Grismayer et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.