Conditional ablation of TGF-β signaling inhibits tumor progression and invasion in an induced mouse bladder cancer model

Sci Rep. 2016 Jul 5:6:29479. doi: 10.1038/srep29479.

Abstract

The role of transforming growth factor-β (TGF-β) signaling in cancer progression is still under debate. To determine the function of TGF-β signaling in bladder cancer progression, we conditionally knocked out the Tgfbr2 in mouse model after a N-butyl-N-4-hydroxybutyl Nitrosamine induced bladder carcinogenesis. We found the ablation of TGF-β signaling could inhibit the cancer cell proliferation, cancer stem cell population and EMT, hence suppressed the invasive cancer progression, which is similar with the result of TGF-β receptor I inhibitor treatment. These findings recognize the roles and mechanisms of TGF-β signaling in bladder cancer progression in vivo for the first time.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Proliferation
  • Disease Models, Animal
  • Disease Progression*
  • Epithelial-Mesenchymal Transition
  • Gene Expression Profiling
  • Male
  • Mice
  • Mice, Knockout
  • Neoplasm Invasiveness
  • Neoplastic Stem Cells / cytology
  • Phosphorylation
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / metabolism*
  • Signal Transduction
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism*
  • Urinary Bladder Neoplasms / metabolism*

Substances

  • Receptors, Transforming Growth Factor beta
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta1
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type I