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Loss of PBRM1 Increases Proliferation and Invasion in Renal Cell Carcinoma by Regulating Chemokine/Chemokine Receptor Interaction Pathway Short Title: PBRM1 and Chemokine Pathways in Kidney Cancer

Login to Access Video or Poster Abstract: MP60-10
Sources of Funding: none

Introduction

PBRM1 is a novel tumor suppressor gene that can inhibit cancer cell proliferation and predict outcome of renal cell carcinoma(RCC), but its biological role still needs further elucidation.

Methods

We examined the expression of the PBRM1 gene in RCC cell lines and the effect of PBRM1 on cell proliferation and invasion in RCC ACHN cells. Microarray processing and analysis was used to explore novel pathways involved in PBRM1 tumorigenesis.

Results

PBRM1 was expressed at high levels in ACHN cells, while lentivirus-mediated PBRM1 knockdown in RCC ACHN cells caused cell-cycle increase in the S phase and dramatically promoted proliferation and invasion in culture. In vivo experiments showed that down expression of PBRM1 could promote tumorigenesis in nude mice. Pathway gene chip analysis revealed that PBRM1 knockdown resulted in the chemokine/chemokine receptor interaction pathway with the most different gene expression. Increased protein levels of IL6ST and CCL2, whereas the protein levels of IL8, IL6 and CXCL2 were decreased.

Conclusions

These findings demonstrate that PBRM1 can alter cell cycle, inhibit proliferation and invasion of ACHN cells through the chemokine/chemokine receptor pathway.

Funding

none

Authors
Hongkai Wang
HaiLiang Zhang
DingWei Ye
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