New insights in CapG induced invasive breast cancer – CapG affects gene expression

Objective: CapG expression is increased in about 30% of breast cancer samples and correlates with migration and invasion potential of tumor cells. Moreover nuclear localization of CapG seems to be important to increase the invasion potential. However the function of CapG in the nucleus is unclear and possible influences on gene expression are discussed. Therefore we performed CapG transcriptome analyses to augment the understanding of the mechanisms.

Material and methods: CapG knock-down and overexpression was performed using siRNA and retroviral transfection, respectively. BioCoat™Matrigel™ was used for the invasion assay and subcellular distribution and CapG protein level were evaluated by immunoblotting. Results of the transcriptome analyses performed by microarrays were correlated with results from microarrays out of cryo-conserved breast cancer samples. For the validation FFPE samples of breast cancer samples were used and analyszed by RT-qPCR.

Results: Invasion potential of breast cancer cell lines correlates with the CapG expression level: CapG knock-down and overexpression leads to a decreased or increase invasive phenotype, respectively. Invasive cell lines showed CapG localization in the nucleus. Microarray analyses of the cell culture model revealed 81 genes regulated in a CapG-dependet manner. Comparing the list of 81 genes with the list of genes revealed by microarray analyses comparing IDC vs. DCIS samples revealed seven genes possibly regulated in a CapG-dependent manner. Gene expression of CapG and gene candidates is increased in IDC compared to DCIS.

Conclusion: CapG regulation of cell motility and effects on gene expression leads to an invasive phenotype of breast cancer.