The gold (III) porphyrin complex, gold-2a, suppresses WNT1 expression in breast cancer cells by enhancing the promoter association of YY1.
作者： Kim Hei-Man Chow , Paul M Vanhoutte , Raymond Wai-Yin Sun , Aimin Xu , Chi-Ming Che
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摘要: The gold (III) porphyrin complex, gold-2a, elicits anti-tumor activity by targeting the Wnt/β-catenin signaling pathway [Chow KH et al, Cancer Research 2010;70(1):329-37]. Here, molecular mechanisms underlying inhibitory effects of this compound on WNT1 gene expression were elucidated further. A response element to gold-2a was identified located within -1290 -1112 nt region promoter, containing a binding site for transcription regulator Yin Yang 1 (YY1). Gold-2a promoted association YY1 and suppressor zeste 12 (Suz12; component polycomb repressor complex 2) with promoter. Under normal culture conditions, intracellular translocalization synchronized cell cycle progression expression. nuclear accumulation abolished exportation YY1, resulting in persistent inhibition arrest at G1/S phase. dimorphic role regulating proliferation division revealed. Thus, present study extends understanding mechanism epigenetic level, which involves modulation dynamic interactions between specific
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