Effect of RUNX2 on some extracellular matrix proteins and enzymes in human breast cancer

Runx2 is one of the runt related genes that are important regulatory molecules of osteoblast/ chondrocyte differentiation. It has recently been discovered that runx2 is overexpressed in human cancers and is one of the major precursors of bone metastasis. In addition, runx2 has been shown to be associated with increased growth, invasion and metastasis in breast, prostate and colorectal cancers. The cancer cell metastasis requires modifications of extracellular matrix (ECM) and reduction in ECM-cell interaction. This process is performed by various enzymes and proteins secreted by cancer cells. Runx2 is responsible for the expression of MMPs which have an important role in ECM modification and ECM-cell interaction. In the light of this information, the effect of runx2 transcription factor on expression of proteins such as osteopontin, SPARC, LOX and heparanase which have important roles in ECM modification and ECM-cell interaction in human breast cancer cell lines were investigated. For this purpose, runx2 knockdown model was created by using runx2 siRNA in human breast cancer oestrogen receptor positive MDA-MB-231 and negative MCF-7 cell lines. The changes in the mRNA and protein expression levels of ECM proteins in this model were shown by the PCR and Western blotting methods respectively. The data obtained from this study showed that there was a decrease in both mRNA and protein levels of HPA1, SPARC and LOX in MCF-7 cells, but there was no change in OPN mRNA and protein levels. However, the protein and mRNA levels of HPA and LOX were significantly reduced in MDA-MB-231 cells and SPARC expression was significantly increased. Consequently, the regulation of matricellular proteins, which are HPA1, LOX and SPARC, expressions through runx2 appears to be one of the regulatory mechanisms of the malignant potential of human breast cancer cells. Therefore, runx2 can be considered as a target molecule in the treatment process of breast cancer.