RRC ID 45403
Author Liu Y, Xu Y, Li X, Chen Z.
Title Smad4 suppresses the progression of renal cell carcinoma via the activation of forkhead box protein H1.
Journal Mol Med Rep
Abstract Smad4 has recently been identified as a tumor suppressor gene in a variety of cancers, yet the role of Smad4 in renal cell carcinoma (RCC) remained to be elusive. Therefore, the aim of the present study was to explore the function of Smad4 in RCC. The expression of Smad4 reduced the growth rate of RCC. The levels of Smad4 and forkhead box protein H1 (FOXH1) mRNA were reduced, while the levels of estrogen receptor were increased in RCC cells compared with those in human renal epithelial cells (P<0.01). Western blot analysis showed an identical trend among the three molecules. Glutathione S‑transferase pull‑down and immunoprecipitation assays proved the interaction between Smad4 and FOXH1. An immunofluorescence assay revealed that Smad4 and FOXH1 were colocalized in the nuclei of RCC cells. Smad4 interacts with Smad2 and migrates into the nucleus, where it interacts with FOXH1 to repress the protein expression of estrogen receptor. These results indicate that Smad4 acts as a tumor suppressor by activating FOXH1, and then suppressing the expression of estrogen receptor, in addition to tumor migration and invasion. Hence, Smad4 should be investigated as a potential target for the treatment for RCC.
Volume 11(4)
Pages 2717-22
Published 2015-4-1
DOI 10.3892/mmr.2014.3061
PMID 25482028
MeSH Adult Aged Carcinoma, Renal Cell / genetics* Carcinoma, Renal Cell / metabolism* Carcinoma, Renal Cell / pathology Case-Control Studies Cell Line, Tumor Cell Proliferation Disease Progression Female Forkhead Transcription Factors / genetics* Forkhead Transcription Factors / metabolism Gene Expression Gene Expression Regulation, Neoplastic Humans Kidney Neoplasms / genetics* Kidney Neoplasms / metabolism* Male Middle Aged Neoplasm Staging Protein Binding Receptors, Estrogen / genetics Receptors, Estrogen / metabolism Risk Factors Smad4 Protein / genetics Smad4 Protein / metabolism* Transcriptional Activation* Transfection
IF 2.1
Times Cited 2
Human and Animal Cells OS-RC-2(RCB0735)