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Updated: Apr 11, 2026

Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
Published on: April 29, 2014
Decrease of phosphorylated proto-oncogene CREB at Ser 133 site inhibits growth and metastatic activity of renal cell
Xue Wang1, Yu Ren, Haihui Zhuang
1Ningbo University, School of Medicine , Ningbo 315211 , China.
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.
Insights
Phosphorylated CREB (pCREB) at Ser 133 drives renal cell carcinoma (RCC) growth and metastasis. Inhibiting pCREB significantly reduces tumor progression and spread, offering a potential therapeutic target for kidney cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Cyclic-AMP-responsive element-binding protein (CREB) is a proto-oncogenic transcription factor implicated in tumor progression.
- Previous studies indicated that blocking the CREB binding site at Ser 133 inhibits target gene expression relevant to cancer.
- The role of phosphorylated CREB (pCREB) at Ser 133 in renal cell carcinoma (RCC) warrants further investigation.
Purpose of the Study:
- To investigate the role of phosphorylated CREB (pCREB) at Ser 133 in the growth and metastasis of renal cell carcinoma (RCC).
- To determine if targeting pCREB at Ser 133 can inhibit RCC progression.
Main Methods:
- Utilized immunohistochemistry, xenograft models in nude mice, and cell-based assays (proliferation, invasion, migration).
- Employed fluorescent immunocytochemistry and Western analysis in an immortalized proximal tubule epithelial cell line and clear-cell RCC.
- Bioinformatic analysis was performed to investigate potential molecular mechanisms.
Main Results:
- Knockdown of pCREB significantly inhibited RCC cell growth in vivo.
- Suppression of pCREB levels reduced cell migration and invasion in vitro, correlating with decreased expression of MMP-2, MMP-9, and EMT-related proteins.
- Vimentin expression and localization remained unchanged, potentially due to the absence of a CRE sequence in its promoter.
Conclusions:
- Decreasing the level of pCREB at Ser 133 effectively inhibits the growth and metastasis of renal cell carcinoma (RCC).
- Targeting the Ser 133 site of pCREB presents a potential therapeutic strategy for managing RCC.
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