PubMed · 2014 · 32 citations · 0 references
Life SciencesMolecular BiologyOncologyCell SignalingMolecular OncologySignal TransductionCancer Cell SignalingHer2-positive Breast CancerHormonal Cancer TherapyReceptor Tyrosine Kinase SignalingRna InterferenceSignal Transduction In CancerCancer Cell Proliferation InhibitionCell Cycle Arrest SignalingCell Cycle TargetsCell Proliferation SuppressionEstrogen Receptor SignalingG1 Phase ArrestHormone Receptor-positive Breast Cancer TherapyLuminal Cells
AIM: We evaluated the potential of TYRO3 as a therapeutic target in various types of breast cancer cell lines. MATERIALS AND METHODS: The effects of TYRO3-knockdown by small interfering RNA (siRNA) on proliferation, cell-cycle distribution, and cell signaling in four estrogen receptor (ER)-positive/HER2-non-amplified (luminal-type), two ER-negative/HER2-amplified (HER2-type), and two ER-negative/HER2-non-amplified (triple negative [TN]-type) cell lines were compared. RESULTS: Whereas TYRO3 knockdown induced the greatest proliferation suppression in luminal-type cells, and to a lesser extent in HER2-type cells, no proliferation inhibition was observed in TN-type cells. The TYRO3 siRNA-induced proliferation inhibition in luminal-type cells was observed in both estradiol (E2)-rich and -null conditions. The proliferation suppression was correlated with G0-G1/S cell-cycle arrest. Western blot analysis showed a decrease in phosphorylation of ERK1/2 or STAT3, and in cyclin D1 only in cell lines sensitive to TYRO3-knockdown. CONCLUSION: TYRO3 is a potential therapeutic target in breast cancer, particularly in luminal-type cells.