title: Zinc-finger protein 545 inhibits cell proliferation as a tumor suppressor through inducing apoptosis and is disrupted by promoter methylation in breast cancer.
abstract: Krüppel-associated box-containing zinc finger proteins (KRAP-ZFPs) are well recognized as key regulators of transcription, which play a crucial role in the regulation of cell proliferation, differentiation, apoptosis and tumorigenesis. We previously identified a KRAP-ZFP protein ZNF545 acting as a tumor suppressor involved in tumor pathogenesis. However, its expression and biological function in breast cancer remain elusive. In this study, we found that ZNF545 was frequently downregulated in estrogen receptor-positive (ER+), progesterone receptor-positive (PR+) and human epidermal growth factor receptor 2-negative (HER2-) breast tumor tissues compared with paired adjacent non-tumor tissues. We further examined its expression and methylation in breast cancer cell lines by semi-quantitative RT-PCR and methylation-specific PCR. We found that ZNF545 was silenced by promoter methylation in MCF7 cell line, and its expression could be restored by demethylation, concomitant with increased unmethylated alleles. ZNF545 methylation was detected in 29% of breast tumor tissues, but not in normal breast tissues, suggesting tumor-specific methylation of ZNF545 in breast cancer. Ectopic expression of ZNF545 in MCF7 cells inhibited cell proliferation through inducing cell cycle G0/G1 arrest and apoptosis, thus as a tumor suppressor. Moreover, ZNF545 upregulated mRNA and protein levels of c-Jun/AP1, BAX, p53 and Caspase 3. Taken together, these results demonstrate that ZNF545 inhibits breast tumor cell proliferation through inducing apoptosis and is disrupted by promoter methylation in breast cancer.
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Tingxiu
authors.initials: T
authors.lastname: Xiang
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xinrong
authors.initials: X
authors.lastname: Luo
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Li
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Weiyan
authors.initials: W
authors.lastname: Peng
authors.affiliation: Cancer Epigenetics Laboratory, Department of Clinical Oncology, State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Li
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Shuman
authors.initials: S
authors.lastname: Li
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Tang
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Ren
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Cancer Epigenetics Laboratory, Department of Clinical Oncology, State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Tao
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D005260:Female; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D051017:Apoptosis Regulatory Proteins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; C579466:ZFP82 protein, human