title: PIAS1 regulates breast tumorigenesis through selective epigenetic gene silencing.
abstract: Epigenetic gene silencing by histone modifications and DNA methylation is essential for cancer development. The molecular mechanism that promotes selective epigenetic changes during tumorigenesis is not understood. We report here that the PIAS1 SUMO ligase is involved in the progression of breast tumorigenesis. Elevated PIAS1 expression was observed in breast tumor samples. PIAS1 knockdown in breast cancer cells reduced the subpopulation of tumor-initiating cells, and inhibited breast tumor growth in vivo. PIAS1 acts by delineating histone modifications and DNA methylation to silence the expression of a subset of clinically relevant genes, including breast cancer DNA methylation signature genes such as cyclin D2 and estrogen receptor, and breast tumor suppressor WNT5A. Our studies identify a novel epigenetic mechanism that regulates breast tumorigenesis through selective gene silencing.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Samuel
authors.initials: S
authors.lastname: Tahk
authors.affiliation: Department of Biological Chemistry, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Yee
authors.affiliation: Department of Biological Chemistry, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Randy
authors.initials: R
authors.lastname: Yang
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Ryan
authors.initials: R
authors.lastname: Mackie
authors.affiliation: Department of General Surgery, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Cary
authors.initials: C
authors.lastname: Hsu
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Vasili
authors.initials: V
authors.lastname: Chernishof
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Neil
authors.initials: N
authors.lastname: O'Brien
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Human Genetics, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Guoping
authors.initials: G
authors.lastname: Fan
authors.affiliation: Department of Obstetrics and Gynecology, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Lane
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Rao
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Dennis
authors.initials: D
authors.lastname: Slamon
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California, United States of America ; Department of Biological Chemistry, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Ke
authors.initials: K
authors.lastname: Shuai
mesh_terms: D000818:Animals; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D056742:Cyclin D2 / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D020868:Gene Silencing; D006801:Humans; D016513:Mice, SCID; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics; D000071818:Wnt-5a Protein
chemical_list: C080336:CCND2 protein, human; D056742:Cyclin D2; C106529:PIAS1 protein, human; D050828:Protein Inhibitors of Activated STAT; D011518:Proto-Oncogene Proteins; D011960:Receptors, Estrogen; D025841:Small Ubiquitin-Related Modifier Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D044767:Ubiquitin-Protein Ligases