<p>Supplementary Figure S4. miR-21 targets 3' UTR of smad7 and PTEN.</p>

<p>Supplementary Figure S1. Myofibroblast differentiation is associated with malignant progression of PTs</p>

<p>Supplementary Figure S4. miR-21 targets 3' UTR of smad7 and PTEN.</p>

<p>Supplementary Figure S6. miR-21 induces myofibroblasts differentiation in breast PTs xenografts.</p>

<p>Supplementary Table S1. Incidence and liver metastasis rate of Tumors from PTs cells in Nude Mice.</p>

<p>Description of additional methods and procedures used in the study.</p>

<p>Supplementary Figure S1. Myofibroblast differentiation is associated with malignant progression of PTs</p>

<p>Supplementary Table S1. Incidence and liver metastasis rate of Tumors from PTs cells in Nude Mice.</p>

<p>Supplementary Figure S2. miR-21 is up-regulated in malignant PTs and correlated with poor prognosis.</p>

<p>Supplementary Figure S3. miR-21 induces myofibroblast differentiation, proliferation and invasion of the stromal cells in PTs.</p>

<p>Description of additional methods and procedures used in the study.</p>

Objective To investigate the expressions of ING4,HIF-1α and HIF-2α in breast cancer tissues and their relationship with tumor angiogenesis.Methods 107 cases of patients with breast cancer undergoing elective surgery were selected.Expressions of HIF-1α,HIF-2α,ING4 and VEGF genes in breast cancer and adjacent tissues were tested by real-time quantitative PCR.The microvessel density (MVD) in breast cancer and adjacent tissues were detected by using immunohistochemical staining.Results The relative expression levels of HIF-1α mRNA and HIF-2α mRNA in breast cancer tissues were higher than the adjacent tissues,while the relative expression levels of ING4 mRNA was lower than the adjacent tissues.The differences were statistically significant (P<0.05).The relative expression levels of HIF-1α mRNA were correlated with lymph node metastasis (P<0.05).The relative expression levels of HIF-2α mRNA were correlated with tumor size and lymph node metastasis (P<0.05),and the relative expression levels of ING4 mRNA were correlated with clinical stage and lymph node metastasis (P<0.05).The relative expression levels of VEGF mRNA and MVD counts in breast cancer tissues were significantly higher than those in adjacent tissues.The differences were statistically significant (P<0.05).Pearson correlation analysis showed that the relative expression levels of HIF-1α mRNA and HIF-2α mRNA were positively correlated with the relative levels of VEGF mRNA and MVD counts (r=0.382,0.417 and 0.408,0.491,P<0.05),and the expression levels of ING4 mRNA in breast cancer tissues were negatively correlated with the relative expression levels of VEGF mRNA and MVD counts (r=-0.395,-0.502,P<0.05).Conclusion The expressions of HIF-1α and HIF-2α genes in breast cancer tissues were up-regulated and ING4 gene was inhibited,which might be involved in the angiogenesis of breast cancer.