Influences in gene expression of transmembrane glycoprotein non-metastatic protein B in breast cancer cells by nuclear macrophage capping protein

Expression of the macrophage capping protein (CapG) is increased in about 30% of breast cancer and correlates with invasion potential of tumor cells. Moreover, nuclear localization of CapG seems to be important to increase the invasion potential. However, its function in the nucleus is unclear. In order to understand CapG's role in the cellular invasion processes its function in transcription should be investigated.

The aim of this study was to perform transcriptome analyses to identify CapG-regulated transcripts.

CapG knock-down and overexpression was performed in breast cancer cell lines using siRNA and retroviral transfection, respectively. Subcellular distribution of CapG protein level was 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 of candidate transcripts FFPE-breast cancer samples were used and analyzed by RT-qPCR.

Invasion potential of breast cancer cell lines correlates with the CapG expression level: CapG knock-down or overexpression decrease or increase cell invasion in vitro, respectively. In invasive cell lines CapG is localized in the nucleus. Microarray analyses revealed 81 genes regulated in a CapG-dependet manner, of which 7 transcripts are more abundant in invasive ductal carcinoma (IDC) compared to ductal carcinoma in situ (DCIS).

Our data suggest that CapG is important for cell invasion which occurs in transition from DCIS to IDC.