SWAP-70: a new type of oncogene

SWAP-70 is a protein that has been suggested to be involved in regulation of actin rearrangement. Having discovered that an artificially-derived mutant of SWAP-70 can transform mouse embryo fibroblasts, we searched for naturally-occurring mutations in the SWAP-70 gene, finding listings for several o...

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Bibliographic Details
Published in:PloS one 2013-03, Vol.8 (3), p.e59245
Main Authors: Shu, Chung-Li, Jing-Yang-Lai, Su, Liang-Cheng, Chuu, Chih-Pin, Fukui, Yasuhisa
Format: Article
Language:English
Subjects:
Actin
Agar
Animals
Biology
Cancer
Cell Communication
Cell Count
Cell growth
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - metabolism
Contact Inhibition
Cytokines
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Embryo fibroblasts
Experiments
Expression vectors
Feedback, Physiological
Fibroblasts
Gene expression
Gene Expression Regulation
Genes
Genetic aspects
Genetic transformation
Genetics
Guanine Nucleotide Exchange Factors - genetics
Guanine Nucleotide Exchange Factors - metabolism
Humans
Immunoglobulins
MAP Kinase Kinase 1 - genetics
MAP Kinase Kinase 1 - metabolism
Medical research
Medicine
Mice
Mice, Nude
Minor Histocompatibility Antigens
Muscle proteins
Mutants
Mutation
NIH 3T3 Cells
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Oncogenes
Ovarian cancer
Parenting
Phosphorylation
Physics
Proteins
Signal Transduction
Signaling
Swaps (Finance)
Transfection
Transformation
Transformed cells
Tumors
Web sites (World Wide Web)
Citations: Items that this one cites
Items that cite this one
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Description
Summary:SWAP-70 is a protein that has been suggested to be involved in regulation of actin rearrangement. Having discovered that an artificially-derived mutant of SWAP-70 can transform mouse embryo fibroblasts, we searched for naturally-occurring mutations in the SWAP-70 gene, finding listings for several on the Web at www.sanger.ac.uk/genetics/CGP/cosmic/, including three mutations found in ovarian cancers. (The number of such mutations has now reached 13 out of 228 tumors). We created expression vectors for the mutant SWAP-70 proteins and introduced these into NIH3T3 cells. The cells expressing the mutant SWAP-70 constructs exhibited faster growth than the parental or wild-type SWAP-70-expressing cells. In most instances, cells that are able to grow in soft agar will form tumors in nude mice. While SWAP-70-transformed cells grew in soft agar, they failed to form tumors in nude mice. This result implies that transformation by the SWAP-70 mutants is unique. The cells bearing the mutant SWAP-70 genes were sensitive to nutrient starvation, supporting the idea that they are transformed cells. However, they failed to pile up and demonstrated contact inhibition, unlike most normal transformed cells. Upon expression of human SWAP-70 genes, MEK1 was activated. This activation appeared to contribute to the saturation density of the cells. As SWAP-70 has been shown to be the last protein to receive signals from cytokines, it is likely that there is a putative feedback signaling pathway, and that disorder of this signaling pathway can transform cells. Accordingly, this may explain why SWAP-70-transformed cells have different characteristics than most transformed cells.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0059245