CapG a putative oncogen affects gene expression in breast cancer cells

The transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) is an important step during breast tumorgenesis. Understanding its molecular changes may uncover both novel preventive and therapeutic strategies and may help to identify high-risk DCIS that progress to IDC. The mechanisms are unknown and the role of CapG in the nucleus is an enigma. Here, we tested the association between clinicopathological CapG expression in tumor samples and used a cell culture model to test the hypothesis that CapG affects gene expression. Breast cancer samples were analyzed by reverse transcriptase – real time PCR (RT-qPCR). We used microarray analysis to study the transcriptome of the cell culture model and validated changes in gene expression in laser capture micro-dissected formalin-fixed paraffin-embedded (FFPE) invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS), respectively. We were able to associate increased CapG expression with an invasive breast cancer phenotype. In 28.2% of breast cancer samples CapG expression in breast cancer samples revealed in 28.2% a very high CapG expression and statistical significant association (p<0.05) to positive metastasis status (M1) and negative ER status (ER-). In case of CapG overexpression microarray analyses generated a list of differential expressed genes and revealed enhanced expression levels of GPNMB, NRP1, LOXL2, TRIM47 and COL16A1, while ZDHHC11, KIAA1467 were down-regulated. We show here for the first time an effect on the transcriptome by experimental modification of CapG expression. Concluding, CapG is involved in tumor progression. CapG expression was modifed in two different breast cancer cell lines (MDA-MB-231 and BT-20), either knock-down (MDA-MB-231) or overexpression (BT-20). Untreated cell lines served as controls. Four independent experiments for each condition were performed.