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Am J Transl Res 2011;3(5):479-491
Original Article
The gold (III) porphyrin complex, gold-2a, suppresses WNT1
expression in breast cancer cells by enhancing the promoter
association of YY1
Kim Hei-Man Chow, Jing Liu, Raymond Wai-Yin Sun, Paul M Vanhoutte, Aimin Xu, Jie Chen, Chi-Ming Che, Yu
Wang
Department of Pharmacology and Pharmacy, Department of Chemistry and Open Laboratory of Chemical Biology
of the Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, Pokfulam,
Hong Kong, China
Received September 30, 2011; accepted October 12, 2011; Epub October 13, 2011; Published October 31, 2011
Abstract: 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, the molecular mechanisms
underlying the inhibitory effects of this compound on WNT1 gene expression were elucidated further. A response
element to gold-2a was identified located within the -1290 to -1112 nt region of the WNT1 promoter, containing a
binding site for the transcription regulator Yin Yang 1 (YY1). Gold-2a promoted the association of YY1 and
suppressor of zeste 12 (Suz12; a component of the polycomb repressor complex 2) with the WNT1 promoter.
Under normal culture conditions, the intracellular translocalization of YY1 was synchronized with cell cycle
progression and WNT1 expression. Gold-2a promoted the nuclear accumulation and abolished the nuclear
exportation of YY1, resulting in a persistent inhibition of WNT1 expression and a cell cycle arrest at G1/S phase. A
dimorphic role of YY1 in regulating cell proliferation and division was revealed. Thus, the present study extends
the understanding of the anti-tumor mechanism of gold-2a to the epigenetic level, which involves the modulation
of the dynamic interactions between YY1 and a specific region of the WNT1 promoter. (AJTR1109005).
Keywords: Gold(III) porphyrin complex, anti-cancer drug, WNT1, YY1, breast cancer
Full Text PDF
Address all correspondence to:
Dr. Yu Wang
Department of Pharmacology and Pharmacy, Faculty of Medicine Building
21 Sassoon Road, Pokfulam, Hong Kong.
Phone: 852-28192864; Fax: 852-28170859
E-mail: yuwanghk@hku.hk
or
Dr. Chi-Ming Che
Department of Chemistry, the University of Hong Kong
Pokfulam Road, Hong Kong.
Phone: 852-28592154; Fax: 852-29155176
E-mail: cmche@hku.hk
Original Article
The gold (III) porphyrin complex, gold-2a, suppresses WNT1
expression in breast cancer cells by enhancing the promoter
association of YY1
Kim Hei-Man Chow, Jing Liu, Raymond Wai-Yin Sun, Paul M Vanhoutte, Aimin Xu, Jie Chen, Chi-Ming Che, Yu
Wang
Department of Pharmacology and Pharmacy, Department of Chemistry and Open Laboratory of Chemical Biology
of the Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, Pokfulam,
Hong Kong, China
Received September 30, 2011; accepted October 12, 2011; Epub October 13, 2011; Published October 31, 2011
Abstract: 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, the molecular mechanisms
underlying the inhibitory effects of this compound on WNT1 gene expression were elucidated further. A response
element to gold-2a was identified located within the -1290 to -1112 nt region of the WNT1 promoter, containing a
binding site for the transcription regulator Yin Yang 1 (YY1). Gold-2a promoted the association of YY1 and
suppressor of zeste 12 (Suz12; a component of the polycomb repressor complex 2) with the WNT1 promoter.
Under normal culture conditions, the intracellular translocalization of YY1 was synchronized with cell cycle
progression and WNT1 expression. Gold-2a promoted the nuclear accumulation and abolished the nuclear
exportation of YY1, resulting in a persistent inhibition of WNT1 expression and a cell cycle arrest at G1/S phase. A
dimorphic role of YY1 in regulating cell proliferation and division was revealed. Thus, the present study extends
the understanding of the anti-tumor mechanism of gold-2a to the epigenetic level, which involves the modulation
of the dynamic interactions between YY1 and a specific region of the WNT1 promoter. (AJTR1109005).
Keywords: Gold(III) porphyrin complex, anti-cancer drug, WNT1, YY1, breast cancer
Full Text PDF
Address all correspondence to:
Dr. Yu Wang
Department of Pharmacology and Pharmacy, Faculty of Medicine Building
21 Sassoon Road, Pokfulam, Hong Kong.
Phone: 852-28192864; Fax: 852-28170859
E-mail: yuwanghk@hku.hk
or
Dr. Chi-Ming Che
Department of Chemistry, the University of Hong Kong
Pokfulam Road, Hong Kong.
Phone: 852-28592154; Fax: 852-29155176
E-mail: cmche@hku.hk
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