BACKGROUND/AIMS: Bone morphogenetic protein-7 (BMP7) has been shown to reduce the severity of injury-induced fibrosis through counteracting the fibrotic effects of transforming growth factor β 1 (TGFβ1). However, this model in the carcinogenesis of breast cancer is unknown. METHODS: We analyzed the effects of BMP7 and TGFβ1 on gene transcripts and protein levels of EMT-related factors in breast cancer cells by RT-qPCR and Western blot, respectively. The effects of BMP7 and TGFβ1 on cell invasiveness and migration were evaluated by scratch wound healing assay and transwell cell migration assay. The cell growth was measured by MTT assay. RESULTS: BMP7 did not alter the TGFβ1-stimulated phosphorylation of TGFβ receptor, but significantly inhibited the TGFβ1-activated epithelial-mesenchymal transition (EMT)-related genes in breast cancer cells, resulting in a significant reduction in TGFβ1-triggered cell growth and cell metastasis. CONCLUSION: Our data suggest that besides being a well-known antagonist for TGFβ1 in fibrosis, BMP7 may also antagonize TGFβ1 in tumorigenesis-associated EMT in breast cancer. Thus, BMP7 may be a promising therapeutic target for treating breast cancer.
BACKGROUND/AIMS: Bone morphogenetic protein-7 (BMP7) has been shown to reduce the severity of injury-induced fibrosis through counteracting the fibrotic effects of transforming growth factor β 1 (TGFβ1). However, this model in the carcinogenesis of breast cancer is unknown. METHODS: We analyzed the effects of BMP7 and TGFβ1 on gene transcripts and protein levels of EMT-related factors in breast cancer cells by RT-qPCR and Western blot, respectively. The effects of BMP7 and TGFβ1 on cell invasiveness and migration were evaluated by scratch wound healing assay and transwell cell migration assay. The cell growth was measured by MTT assay. RESULTS:BMP7 did not alter the TGFβ1-stimulated phosphorylation of TGFβ receptor, but significantly inhibited the TGFβ1-activated epithelial-mesenchymal transition (EMT)-related genes in breast cancer cells, resulting in a significant reduction in TGFβ1-triggered cell growth and cell metastasis. CONCLUSION: Our data suggest that besides being a well-known antagonist for TGFβ1 in fibrosis, BMP7 may also antagonize TGFβ1 in tumorigenesis-associated EMT in breast cancer. Thus, BMP7 may be a promising therapeutic target for treating breast cancer.
Authors: Yang Gao; Allison Jones; Peter A Fasching; Matthias Ruebner; Matthias W Beckmann; Martin Widschwendter; Andrew E Teschendorff Journal: Clin Epigenetics Date: 2015-12-09 Impact factor: 6.551