Responses of breast cancer lines to growth factors

Analysis of growth factor signaling in genetically diverse breast cancer lines

Mario Niepel1*, Marc Hafner1*, Emily A. Pace2*, Mirra Chung1, Diana H. Chai2, Lili Zhou1, Jeremy L. Muhlich1, Birgit Schoeberl2 and Peter K. Sorger1

1HMS LINCS Center; 2Merrimack Pharmaceuticals

doi:10.1186/1741-7007-12-20

Synopsis

Growth factor signaling is a key determinant of cellular behavior in normal and diseased tissue. Here we determined the variance of signaling responses across a panel of breast cancer lines and identified potential molecular underpinnings of these responses. We correlated basal receptors levels with ligand responses to derive a simple heuristic that approximates the responsiveness of cells to individual growth factors.

  • We analyzed the response of 39 breast cancer cell lines to 15 ligands at 2 doses, 3 time points by measuring pERK and pAKT levels and we related these responses to clinical cancer subtypes and the expression and phosphorylation levels of RTKs.
  • The response to ErbB ligands is ubiquitous across virtually all cell lines and many respond to HGF, FGFs, and IGF/INS.
  • TNBCs are highly responsive to a variety of ligands, while HER2amp cell lines only show muted responses.
  • The responsiveness of individual cell lines can be determined by a simple heuristic.
  • We published an interactive website to browse the data by cell lines and ligands (version at the time of publication).

Key datasets

1. Kinetic cluster of the ligand responses Details Download (.xls)
2. Sensitivity class for ligand responses Details Download (.xls)
3. All ligand responses (Data from Sci. Signal., 2013, Vol. 6, ra84) Details Download (.xls)
4. All basal levels (Data from Sci. Signal., 2013, Vol. 6, ra84) Details Download (.xls)