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

Background Rab 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. Re...

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Vydané v:	Molecular cancer Ročník 11; číslo 1; s. 62
Hlavní autori:	Grismayer, Bettina, Sölch, Susanne, Seubert, Bastian, Kirchner, Thomas, Schäfer, Sonja, Baretton, Gustavo, Schmitt, Manfred, Luther, Thomas, Krüger, Achim, Kotzsch, Matthias, Magdolen, Viktor
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London BioMed Central 24.08.2012 BioMed Central Ltd Springer Nature B.V BMC
Predmet:	Adhesion Amino acids Analysis Animals Antibodies - immunology Antibodies - metabolism Binding proteins Biomedical and Life Sciences Biomedicine Breast cancer Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Cancer Cancer cells Cancer Research Cell Adhesion Cell adhesion & migration Cell Line, Tumor Cell Movement Cell Proliferation Cellular proteins Colleges & universities Development and progression Disease Models, Animal Enzyme-linked immunosorbent assay Estrogen Extracellular Matrix Proteins - metabolism Female Gene Expression Gene Expression Regulation, Neoplastic Genetic aspects GTP-binding protein Humans Intracellular vesicle transport Invasion Metastasis Mice Mice, Nude Oncology Oncology, Experimental Physiological aspects Polyclonal antibodies Prognosis Proliferation Protein binding Proteins rab GTP-Binding Proteins - genetics rab GTP-Binding Proteins - immunology rab GTP-Binding Proteins - metabolism rab31 RNA Rodents Transplantation, Heterologous Tumor cell phenotype Germany GTP-binding protein Tumor cell phenotype rab31 Intracellular vesicle transport Breast cancer Proliferation Adhesion Invasion
ISSN:	1476-4598, 1476-4598
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Shrnutí:	Background Rab 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 . Methods Breast 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. Results Elevated 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 Matrigel TM . 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. Conclusions Overexpression 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 .
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1476-4598 1476-4598
DOI:	10.1186/1476-4598-11-62