title: PLCD1 is a functional tumor suppressor inducing G(2)/M arrest and frequently methylated in breast cancer.
abstract: Chromosome 3p harbors multiple tumor-suppressor genes. PLCD1, located at 3p22, encodes an enzyme that mediates regulatory signaling of energy metabolism, calcium homeostasis and intracellular movement. We investigated the epigenetic alterations of PLCD1 and its tumor suppressor function in breast cancer. Frequent downregulation/silencing of PLCD1 was shown in most breast cancer cell lines by using semi-quantitative PCR. Promoter methylation of PLCD1 was detected in 78% (7/9) of cell lines and 52% (13/25) of primary tumors by Methylation-specific PCR (MSP), but not in any tumor adjacent breast tissues and normal breast tissues, which was further confirmed by bisulfite genomic sequencing (BGS). The silencing of PLCD1 could be reversed by pharmacological demethylation, indicating a methylation-mediated mechanism. Ectopic expression of PLCD1 in silenced breast cancer cells significantly inhibited their colony formation. In addition, PLCD1 inhibited tumor cell migration and induced cell cycle G(2)/M arrest. Thus, this study for the first time demonstrates the frequent inactivation of PLCD1 by promoter methylation and its tumor inhibitory function in breast cancer. Tumor-specific methylation of PLCD1 might serve as a biomarker for possible early detection and prognosis prediction of breast cancer.
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Tingxiu
authors.initials: T
authors.lastname: Xiang
authors.forename: Lili
authors.initials: L
authors.lastname: Li
authors.forename: Yichao
authors.initials: Y
authors.lastname: Fan
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Ying
authors.initials: Y
authors.lastname: Ying
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Putti
authors.forename: Qian
authors.initials: Q
authors.lastname: Tao
authors.forename: Guosheng
authors.initials: G
authors.lastname: Ren
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D045744:Cell Line, Tumor; D002893:Chromosomes, Human, Pair 3; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D016195:G2 Phase; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D054803:Phospholipase C delta / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D025521:Tumor Suppressor Proteins; C518024:PLCD1 protein, human; D054803:Phospholipase C delta