title: Epigenetic activation of LY6K predicts the presence of metastasis and poor prognosis in breast carcinoma.
abstract: The role of lymphocyte antigen 6 complex, locus K (LY6K) in breast cancer has been studied, whereas the epigenetic control of LY6K transcription is not fully understood. Here, we report that breast cancer patients with increased LY6K expression had shorter disease-free and overall survival than the patients with low levels of LY6K by multivariate analysis. LY6K also was upregulated in breast cancer patients with distant metastases than those without distant metastases, downregulating E-cadherin expression. Furthermore, xenograft tumor volumes from LY6K knockdown nude mice were reduced than those of mice treated with control lentivirus. Interestingly, LY6K has a CpG island (CGI) around the transcription start site and non-CGI in its promoter, called a CGI shore. LY6K expression was inversely correlated with methylation in not only CGI but CGI shore, which are associated with histone modifications. Additionally, LY6K methylation was increased by the PAX3 transcription factor due to the SNP242 mutation in LY6K CGI shore. Taken together, breast cancer risk and metastasis were significantly associated with not only LY6K expression, but also methylation of CGI shore which induced by SNP242 mutation. Our results suggest that an understanding epigenetic mechanism of the LY6K gene may be useful to diagnose carcinogenic risk and predict outcomes of patients with metastatic breast cancer.
authors: Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea.
authors: Hyun Kyung
authors: HK
authors: Kong
authors: Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea.
authors: Sae Jeong
authors: SJ
authors: Park
authors: Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea.
authors: Ye Sol
authors: YS
authors: Kim
authors: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors: Kyoung Min
authors: KM
authors: Kim
authors: Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Republic of Korea.|Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
authors: Hyun-Woo
authors: HW
authors: Lee
authors: Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Republic of Korea.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors: Hyeok-Gu
authors: HG
authors: Kang
authors: Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea.
authors: Yu Mi
authors: YM
authors: Woo
authors: Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea.
authors: Eun Young
authors: EY
authors: Park
authors: Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea.
authors: Je Yeong
authors: JY
authors: Ko
authors: Department of Molecular Biology, Sapporo Medical University, Sapporo, Japan.
authors: Hiromu
authors: H
authors: Suzuki
authors: Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Republic of Korea.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors: Kyung-Hee
authors: KH
authors: Chun
authors: Department of Breast Surgery, Sun Yat-Sen Memorial Hospital, Sun-Yat-Sen University, Guangzhou, Peoples Republic of China.
authors: Erwei
authors: E
authors: Song
authors: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors: Kyu Yun
authors: KY
authors: Jang
authors: Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea.
authors: Jong Hoon
authors: JH
authors: Park
mesh_terms: D000818:Animals; D015703:Antigens, CD; D000950:Antigens, Ly / Q000235:genetics*; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology*; D015820:Cadherins / Q000032:analysis; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D011379:Prognosis; D011401:Promoter Regions, Genetic
chemical_list: D015703:Antigens, CD; D000950:Antigens, Ly; C513384:CDH1 protein, human; D015820:Cadherins; D058851:GPI-Linked Proteins; C525725:LY6K protein, human
keywords: DNA methylation; LY6K; breast cancer; histone modification; metastasis