Wysokinski Daniel, Blasiak Janusz, Pawlowska Elzbieta
Department of Molecular Genetics, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
Department of Orthodontics, Medical University of Lodz, Pomorska 251, 92-216 Lodz, Poland.
Int J Mol Sci. 2015 Sep 2;16(9):20969-93. doi: 10.3390/ijms160920969.
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.
RUNX2是一种在成骨过程中起主要作用的转录因子，但它可参与DNA损伤反应，而这对癌症转化至关重要。RUNX2可与细胞周期调节因子相互作用：细胞周期蛋白依赖性激酶、pRB和p21Cip1蛋白，以及细胞周期的主要调节因子p53肿瘤抑制因子。RUNX2参与许多信号通路，包括对雌激素信号传导重要的那些通路，而雌激素信号传导反过来对乳腺癌发生也很重要。RUNX2可通过Wnt和Tgfβ信号通路促进乳腺癌发展，尤其是在雌激素受体（ER）阴性的病例中。ERα直接与RUNX2相互作用并调节其活性。此外，ERα基因在其启动子内有一个RUNX2结合位点。RUNX2刺激芳香化酶（一种产生雌激素的酶）的表达，增加雌激素水平，进而刺激细胞增殖和复制错误，而这些错误可转化为致癌突变。探索RUNX2在乳腺癌发病机制中的作用可有助于揭示新的治疗靶点。
