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Global gene expression profiling of cells overexpressing SMC3

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Author(s): Ghiselli Giancarlo | Liu Chang-Gong

Journal: Molecular Cancer
ISSN 1476-4598

Volume: 4;
Issue: 1;
Start page: 34;
Date: 2005;
Original page

ABSTRACT
Abstract Background The Structural Maintenance of Chromosome 3 protein (SMC3) plays an essential role during the sister chromatid separation, is involved in DNA repair and recombination and participates in microtubule-mediated intracellular transport. SMC3 is frequently elevated in human colon carcinoma and overexpression of the protein transforms murine NIH3T3 fibroblasts. In order to gain insight into the mechanism of SMC3-mediated tumorigenesis a gene expression profiling was performed on human 293 cells line stably overexpressing SMC3. Results Biotinylated complementary RNA (cRNA) was used for hybridization of a cDNAmicroarray chip harboring 18,861 65-mer oligos derived from the published dEST sequences. After filtering, the hybridization data were normalized and statistically analyzed. Sixty-five genes for which a putative function could be assigned displayed at least two-fold change in their expression level. Eighteen of the affected genes is either a transcriptional factor or is involved in DNA and chromatin related mechanisms whereas most of those involved in signal transduction are members or modulators of the ras-rho/GTPase and cAMP signaling pathways. In particular the expression of RhoB and CRE-BPa, two mediators of cellular transformation, was significantly enhanced. This association was confirmed by analyzing the RhoB and CRE-BPa transcript levels in cells transiently transfected with an SMC3 expression vector. Consistent with the idea that the activation of ras-rho/GTPase and cAMP pathways is relevant in the context of the cellular changes following SMC3 overexpression, gene transactivation through the related serum (SRE) and cAMP (CRE) cis-acting response elements was significantly increased. Conclusion We have documented a selective effect of the ectopic expression of SMC3 on a set of genes and transcriptional signaling pathways that are relevant for tumorigenesis. The results lead to postulate that RhoB and CRE-BPa two known oncogenic mediators whose expression is significantly increased following SMC3 overexpression play a significant role in mediating SMC3 tumorigenesis.

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