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Expression profiling of Ral-depleted bladder cancer cells identifies RREB-1 as a novel transcriptional Ral effector

Oncogene volume 26, pages 7143–7152 (2007)Cite this article

Abstract

Although the monomeric GTPases RalA and RalB have been shown to regulate a variety of transcription factors, little is known regarding the differences or similarities in transcriptional programs regulated by RalA compared to RalB. Further, the association of these transcriptional pathways to human carcinogenesis and progression remains unclear. Here, we studied the role of RalA and/or RalB in transcriptional regulation by combining short interfering RNA depletion of Ral with gene expression profiling via microarray in the human bladder cancer cell line, UMUC-3. A large number of genes were found to be similarly modulated in cells with RalA and RalB depletion, suggesting that RalA and RalB impinge on overlapping transcriptional signaling pathways. However, smaller sets of genes were modulated by depletion of RalA or RalB, indicating that these closely related proteins also regulate nonoverlapping transcriptional pathways. Computational analysis of upstream sequences of genes modulated by Ral depletion identified Ras-responsive element-binding protein (RREB)-1, as a putative Ral transcriptional target, which we verified experimentally. Importantly, as a group, Ral-regulated probe sets identified here were disproportionally represented among those differentially expressed as a function of human bladder transformation. Taken together, these data strongly suggest that Ral family members mediate both common and specific transcriptional programs that are associated with human cancer and identify RREB-1 as a novel transcriptional effector of Ral.

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Acknowledgements

This work was supported by Medical Scientist Training Program training grant T32GM007267 to SCS, Cancer Training Grant CA009109-29 to SCS, and CA075115 and PO1CA104106 to DT.

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Authors and Affiliations

  1. Department of Molecular Physiology and Biological Physics, Health Sciences Center, University of Virginia, Charlottesville, VA, USA

    G Oxford, S C Smith & D Theodorescu

  2. Genomics Institute of the Novartis Research Foundation, San Diego, CA, USA

    G Hampton

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  1. G Oxford
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  2. S C Smith
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  3. G Hampton
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  4. D Theodorescu
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Correspondence to D Theodorescu.

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These authors state no conflict of interest.

Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Oxford, G., Smith, S., Hampton, G. et al. Expression profiling of Ral-depleted bladder cancer cells identifies RREB-1 as a novel transcriptional Ral effector. Oncogene 26, 7143–7152 (2007). https://doi.org/10.1038/sj.onc.1210521

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