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Int. J. Mol. Sci. 2015, 16(9), 20969-20993; doi:10.3390/ijms160920969

Role of RUNX2 in Breast Carcinogenesis

1
Department of Molecular Genetics, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland
2
Department of Orthodontics, Medical University of Lodz, Pomorska 251, 92-216 Lodz, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 30 July 2015 / Revised: 14 August 2015 / Accepted: 20 August 2015 / Published: 2 September 2015
(This article belongs to the Collection Advances in Molecular Oncology)
View Full-Text   |   Download PDF [1213 KB, uploaded 2 September 2015]   |  

Abstract

RUNX2 is a transcription factor playing the major role in osteogenesis, but it can be involved in DNA damage response, which is crucial for cancer transformation. RUNX2 can interact with cell cycle regulators: cyclin-dependent kinases, pRB and p21Cip1 proteins, as well as the master regulator of the cell cycle, the p53 tumor suppressor. RUNX2 is involved in many signaling pathways, including those important for estrogen signaling, which, in turn, are significant for breast carcinogenesis. RUNX2 can promote breast cancer development through Wnt and Tgfβ signaling pathways, especially in estrogen receptor (ER)-negative cases. ERα interacts directly with RUNX2 and regulates its activity. Moreover, the ERa gene has a RUNX2 binding site within its promoter. RUNX2 stimulates the expression of aromatase, an estrogen producing enzyme, increasing the level of estrogens, which in turn stimulate cell proliferation and replication errors, which can be turned into carcinogenic mutations. Exploring the role of RUNX2 in the pathogenesis of breast cancer can lead to revealing new therapeutic targets. View Full-Text
Keywords: RUNX2; estrogen; breast cancer; DNA damage response; cell cycle RUNX2; estrogen; breast cancer; DNA damage response; cell cycle
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Wysokinski, D.; Blasiak, J.; Pawlowska, E. Role of RUNX2 in Breast Carcinogenesis. Int. J. Mol. Sci. 2015, 16, 20969-20993.

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