title: DNMT3B7 expression promotes tumor progression to a more aggressive phenotype in breast cancer cells.
abstract: Epigenetic changes, such as DNA methylation, have been shown to promote breast cancer progression. However, the mechanism by which cancer cells acquire and maintain abnormal DNA methylation is not well understood. We have previously identified an aberrant splice form of a DNA methyltransferase, DNMT3B7, expressed in virtually all cancer cell lines but at very low levels in normal cells. Furthermore, aggressive MDA-MB-231 breast cancer cells have been shown to express increased levels of DNMT3B7 compared to poorly invasive MCF-7 cells, indicating that DNMT3B7 may have a role in promoting a more invasive phenotype. Using data gathered from The Cancer Genome Atlas, we show that DNMT3B7 expression is increased in breast cancer patient tissues compared to normal tissue. To determine the mechanism by which DNMT3B7 was functioning in breast cancer cells, two poorly invasive breast cancer cell lines, MCF-7 and T-47D, were stably transfected with a DNMT3B7 expression construct. Expression of DNMT3B7 led to hypermethylation and down-regulation of E-cadherin, altered localization of β-catenin, as well as increased adhesion turnover, cell proliferation, and anchorage-independent growth. The novel results presented in this study suggest a role for DNMT3B7 in the progression of breast cancer to a more aggressive state and the potential for future development of novel therapeutics.
authors.affiliation: Department of Biology, Elmhurst College, Elmhurst, Illinois, United States of America.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Brambert
authors.affiliation: Department of Biology, Elmhurst College, Elmhurst, Illinois, United States of America.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kelpsch
authors.affiliation: Department of Biology, Elmhurst College, Elmhurst, Illinois, United States of America.
authors.forename: Rabia
authors.initials: R
authors.lastname: Hameed
authors.affiliation: Department of Biology, Elmhurst College, Elmhurst, Illinois, United States of America.
authors.forename: Charmi V
authors.initials: CV
authors.lastname: Desai
authors.affiliation: Department of Biology, Elmhurst College, Elmhurst, Illinois, United States of America.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Calafiore
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Godley
authors.affiliation: Department of Biology, Elmhurst College, Elmhurst, Illinois, United States of America.
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Raimondi
mesh_terms: D017398:Alternative Splicing; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D008745:Methylation; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation; D051176:beta Catenin / Q000378:metabolism; D000097584:DNA Methyltransferase 3B
chemical_list: D015820:Cadherins; D004248:DNA (Cytosine-5-)-Methyltransferases; D012333:RNA, Messenger; D051176:beta Catenin; D000097584:DNA Methyltransferase 3B