Role of RUNX2 in mitogen-activated protein kinase (MAPK) mediated cell proliferation of breast cancer cells.
Date of Issue2009
School of Biological Sciences
Oncology Research Institute
RUNX2 is a key regulator of bone development and it controls genes that contribute to cell growth regulation in osteoblast. This study investigated the role that RUNX2 play in the cell proliferation regulatory pathways of breast cancer cells. From our serum stimulation study of MDA-MB-231 cells, results showed that RUNX2 protein levels decreased and proliferation of breast cancer cells was enhanced. Our quantitative RT-PCR results showed approximately 5-fold higher levels of cyclin D1 in MDA-MB-231 cells with knockdown of RUNX2; further suggest the involvement of RUNX2 in inhibiting cell proliferation. ERK pathway is the best characterized MAPK pathway in mammalian cells, which plays a key role in cell proliferation. From our study, we showed that ERK pathway is also involved in the upstream regulation of RUNX2 in breast cancer cells. MDA-MB-231 cells were treated with MEK1 inhibitor PD98059 and results showed a gradual decrease in ERK1/2 phosphorylation and also a modest increase in RUNX2 protein level. From this study, we showed an inverse correlation between ERK1/2 phosphorylation and RUNX2 protein level. In conclusion this study suggested that RUNX2 may inhibit cell proliferation in breast cancer cells and its level is regulated by ERK pathway.
Final Year Project (FYP)
Nanyang Technological University