Attenuation of TGF-β signaling supports tumor progression of a mesenchymal-like mammary tumor cell line in a syngeneic murine model

Cancer Lett. 2014 Apr 28;346(1):129-38. doi: 10.1016/j.canlet.2013.12.018. Epub 2013 Dec 22.


Previous studies have suggested that TGF-β functions as a tumor promoter in metastatic, mesenchymal-like breast cancer cells and that TGF-β inhibitors can effectively abrogate tumor progression in several of these models. Here we report a novel observation with the use of genetic and pharmacological approaches, and murine mammary cell injection models in both syngeneic and immune compromised mice. We found that TGF-β receptor II (TβRII) knockdown in the MMTV-PyMT derived Py8119, a mesenchymal-like murine mammary tumor cell line, resulted in increased orthotopic tumor growth potential in a syngeneic background and a similar trend in an immune compromised background. Systemic treatment with a small-molecule TGF-β receptor I kinase inhibitor induced a trend towards increased metastatic colonization of distant organs following intracardiac inoculation of Py8119 cells, with little effect on the colonization of luminal-like Py230 cells, also derived from MMTV-PyMT tumors. Taken together, our data suggest that the attenuation of TGF-β signaling in mesenchymal-like mammary tumors does not necessarily inhibit their malignant potential, and anti-TGF-β therapeutic intervention requires greater precision in identifying molecular markers in tumors with an indication of functional TGF-β signaling.

Keywords: MMTV-PyMT mammary tumor; Metastasis; Syngeneic model; TGF-β.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line, Tumor
  • Disease Progression
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Female
  • Immunohistochemistry
  • Mammary Neoplasms, Experimental / metabolism*
  • Mammary Neoplasms, Experimental / pathology*
  • Mesoderm / metabolism
  • Mesoderm / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Phenotype
  • Protein Kinase Inhibitors / pharmacology
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / physiology*
  • Transforming Growth Factor beta / metabolism*


  • Protein Kinase Inhibitors
  • Transforming Growth Factor beta