A Human Bone Morphogenetic Protein Antagonist Is Down-Regulated in Renal Cancer
Open Access
- 1 February 2008
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 19 (2), 457-464
- https://doi.org/10.1091/mbc.e07-05-0433
Abstract
We analyzed expression of candidate genes encoding cell surface or secreted proteins in normal kidney and kidney cancer. This screen identified a bone morphogenetic protein (BMP) antagonist, SOSTDC1 (sclerostin domain–containing-1) as down-regulated in kidney tumors. To confirm screening results, we probed cDNA dot blots with SOSTDC1. The SOSTDC1 message was decreased in 20/20 kidney tumors compared with normal kidney tissue. Immunohistochemistry confirmed significant decrease of SOSTDC1 protein in clear cell renal carcinomas relative to normal proximal renal tubule cells (p < 0.001). Expression of SOSTDC1 was not decreased in papillary and chromophobe kidney tumors. SOSTDC1 was abundantly expressed in podocytes, distal tubules, and transitional epithelia of the normal kidney. Transfection experiments demonstrated that SOSTDC1 is secreted and binds to neighboring cells and/or the extracellular matrix. SOSTDC1 suppresses both BMP-7–induced phosphorylation of R-Smads-1, -5, and -8 and Wnt-3a signaling. Restoration of SOSTDC1 in renal clear carcinoma cells profoundly suppresses proliferation. Collectively, these results demonstrate that SOSTDC1 is expressed in the human kidney and decreased in renal clear cell carcinoma. Because SOSTDC1 suppresses proliferation of renal carcinoma cells, restoration of SOSTDC1 signaling may represent a novel target in treatment of renal clear cell carcinoma.Keywords
This publication has 45 references indexed in Scilit:
- Bone morphogenetic protein antagonist gremlin 1 is widely expressed by cancer-associated stromal cells and can promote tumor cell proliferationProceedings of the National Academy of Sciences of the United States of America, 2006
- Modulator of bone morphogenetic protein activity in the progression of kidney diseasesKidney International, 2006
- Bone morphogenetic proteins in melanoma: Angel or devil?Cancer and Metastasis Reviews, 2005
- Bone Morphogenetic ProteinsGrowth Factors, 2004
- USAG-1: a bone morphogenetic protein antagonist abundantly expressed in the kidneyBiochemical and Biophysical Research Communications, 2004
- Zebrafish Prickle, a Modulator of Noncanonical Wnt/Fz Signaling, Regulates Gastrulation MovementsCurrent Biology, 2003
- BMP-7-Induced Cell Cycle Arrest of Anaplastic Thyroid Carcinoma Cells via p21CIP1 and p27KIP1Biochemical and Biophysical Research Communications, 2001
- Divergence and convergence of TGF‐β/BMP signalingJournal of Cellular Physiology, 2001
- Bone Morphogenetic Protein-2 Blocks MDA MB 231 Human Breast Cancer Cell Proliferation by Inhibiting Cyclin-Dependent Kinase-Mediated Retinoblastoma Protein PhosphorylationBiochemical and Biophysical Research Communications, 2000
- The bone morphogenetic protein family and osteogenesisMolecular Reproduction and Development, 1992