1. Opposing roles of TGFβ and BMP signaling in prostate cancer development
- Author
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Eun-Jung Jin, Xi Cheng, Y. Alan Wang, Pingna Deng, Shan Feng, Xiaoying Shang, Sharif Rahmy, Ronald A. DePinho, Xin Lu, Shan Jiang, Ren Zhao, Qing Chang, Xuemin Lu, and Seema Chaudhary
- Subjects
Male ,0301 basic medicine ,Genotype ,Bone Neoplasms ,Kaplan-Meier Estimate ,Protein Serine-Threonine Kinases ,Bone Morphogenetic Protein Receptors, Type II ,Bone morphogenetic protein ,Mice ,Research Communication ,03 medical and health sciences ,Prostate cancer ,Genetics ,medicine ,Animals ,PTEN ,Receptor ,Smad4 Protein ,biology ,Gene Expression Profiling ,PTEN Phosphohydrolase ,Receptor, Transforming Growth Factor-beta Type II ,Prostatic Neoplasms ,Bone metastasis ,medicine.disease ,BMPR2 ,Gene Expression Regulation, Neoplastic ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,biology.protein ,Cancer research ,Signal transduction ,Receptors, Transforming Growth Factor beta ,Gene Deletion ,Signal Transduction ,Developmental Biology ,Transforming growth factor - Abstract
SMAD4 constrains progression of Pten-null prostate cancer and serves as a common downstream node of transforming growth factor β (TGFβ) and bone morphogenetic protein (BMP) pathways. Here, we dissected the roles of TGFβ receptor II (TGFBR2) and BMP receptor II (BMPR2) using a Pten-null prostate cancer model. These studies demonstrated that the molecular actions of TGFBR2 result in both SMAD4-dependent constraint of proliferation and SMAD4-independent activation of apoptosis. In contrast, BMPR2 deletion extended survival relative to Pten deletion alone, establishing its promoting role in BMP6-driven prostate cancer progression. These analyses reveal the complexity of TGFβ–BMP signaling and illuminate potential therapeutic targets for prostate cancer.
- Published
- 2017