Sam68 haploinsufficiency delays onset of mammary tumorigenesis and metastasis

Oncogene. 2008 Jan 17;27(4):548-56. doi: 10.1038/sj.onc.1210652. Epub 2007 Jul 9.


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

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / physiology*
  • Animals
  • Antigens, Viral, Tumor / genetics
  • CSK Tyrosine-Protein Kinase
  • Cell Proliferation
  • Enzyme Activation / genetics
  • Female
  • Focal Adhesion Kinase 2 / metabolism
  • Heterozygote*
  • Lung Neoplasms / secondary
  • Mammary Glands, Animal / abnormalities
  • Mammary Glands, Animal / growth & development
  • Mammary Neoplasms, Experimental / genetics*
  • Mammary Neoplasms, Experimental / pathology*
  • Mice
  • Mice, Knockout
  • Neoplasm Metastasis
  • Polyomavirus / genetics
  • Protein-Tyrosine Kinases / metabolism
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / physiology*
  • Signal Transduction / genetics
  • Time Factors
  • Tumor Burden / genetics
  • Tumor Cells, Cultured
  • Uterus / abnormalities
  • Uterus / growth & development
  • src-Family Kinases


  • Adaptor Proteins, Signal Transducing
  • Antigens, Viral, Tumor
  • Khdrbs1 protein, mouse
  • RNA-Binding Proteins
  • Protein-Tyrosine Kinases
  • CSK Tyrosine-Protein Kinase
  • Focal Adhesion Kinase 2
  • src-Family Kinases