Abstract
The Src-associated substrate in mitosis Sam68 is a KH type RNA-binding protein known to be a substrate of numerous tyrosine kinases, and often referred to as a STAR (signal transduction activator of RNA) protein. Herein, we observed that Sam68-null mice display mammary gland and the uterine development defects. Moreover, we report that Sam68 haploinsufficiency impedes mammary tumor onset in vivo driven by the potent mammary-targeted polyoma middle T-antigen (MMTV-PyMT) oncogene. The effect was cell autonomous as the Sam68 knockdown in PyMT-transformed cell lines also delayed tumorigenesis and metastasis formation in nude mice. Interestingly, tumor extracts isolated from PyMT/Sam68(+/-) mice compared with PyMT/Sam68(+/+) mice contained activated Src and FAK kinases. These findings suggest that Sam68 may be a modulator of tyrosine kinase activity in vivo and a signaling requirement for mammary tumorigenesis and metastasis.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics*
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Adaptor Proteins, Signal Transducing / physiology*
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Animals
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Antigens, Viral, Tumor / genetics
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CSK Tyrosine-Protein Kinase
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Cell Proliferation
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Enzyme Activation / genetics
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Female
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Focal Adhesion Kinase 2 / metabolism
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Heterozygote*
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Lung Neoplasms / secondary
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Mammary Glands, Animal / abnormalities
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Mammary Glands, Animal / growth & development
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Mammary Neoplasms, Experimental / genetics*
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Mammary Neoplasms, Experimental / pathology*
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Mice
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Mice, Knockout
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Neoplasm Metastasis
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Polyomavirus / genetics
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Protein-Tyrosine Kinases / metabolism
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RNA-Binding Proteins / genetics*
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RNA-Binding Proteins / physiology*
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Signal Transduction / genetics
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Time Factors
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Tumor Burden / genetics
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Tumor Cells, Cultured
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Uterus / abnormalities
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Uterus / growth & development
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src-Family Kinases
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, Viral, Tumor
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Khdrbs1 protein, mouse
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RNA-Binding Proteins
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Protein-Tyrosine Kinases
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CSK Tyrosine-Protein Kinase
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Focal Adhesion Kinase 2
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src-Family Kinases