title: Decrease of phosphorylated proto-oncogene CREB at Ser 133 site inhibits growth and metastatic activity of renal cell cancer.
abstract: OBJECTIVE
  Cyclic-AMP-responsive element-binding protein (CREB) is a proto-oncogenic transcription factor. The authors' previous reports showed that blocking the CREB binding site at Ser 133 inhibited the expression of target genes, which related to the progression of some tumors. In this study, the authors investigated the role of phosphorylated CREB (pCREB) at Ser133 in renal cell carcinoma (RCC) growth and metastases.
  
  
  METHODS
  Immunohistochemistry, xenograft model in nude mice, cell proliferation assay, cell invasion/migration assay, fluorescent immunocytochemistry and Western analysis were performed in an immortalized proximal tubule epithelial cell line and clear-cell RCC.
  
  
  RESULTS
  The authors' results showed that knockdown of pCREB inhibited kidney cancer cells growth in vivo. Furthermore, suppression of the pCREB level blunted the capabilities of cell migration and invasion in vitro and was accompanied with significantly decreased expression of MMP-2 and MMP-9, the filopodia formation and epithelial-mesenchymal transition-related proteins. Surprisingly, no changes of expression or location of vimentin were revealed in the experiment. Bioinformatic software explained the possible reason for this is that the promoter of vimentin does not contain the CRE sequence.
  
  
  CONCLUSIONS
  These data suggest that decreasing the level of pCREB inhibits the growth and metastasis of RCC by targeting the Ser 133 site.
authors.affiliation: Ningbo University, School of Medicine , Ningbo 315211 , China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Ren
authors.forename: Haihui
authors.initials: H
authors.lastname: Zhuang
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Meng
authors.forename: Shuaishuai
authors.initials: S
authors.lastname: Huang
authors.forename: Yanyuan
authors.initials: Y
authors.lastname: Li
authors.forename: Michael
authors.initials: M
authors.lastname: Hehir
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D055785:Gene Knockdown Techniques; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D014746:Vimentin / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D014746:Vimentin
keywords: cyclic-AMP-responsive element-binding protein; growth; metastasis; renal cell cancer