title: Reduced PDEF expression increases invasion and expression of mesenchymal genes in prostate cancer cells.
abstract: The epithelium-specific Ets transcription factor, PDEF, plays a role in prostate and breast cancer, although its precise function has not been established. In prostate cancer, PDEF is involved in regulating prostate-specific antigen expression via interaction with the androgen receptor and NKX3.1, and down-regulation of PDEF by antiproliferative agents has been associated with reduced PDEF expression. We now report that reduced expression of PDEF leads to a morphologic change, increased migration and invasiveness in prostate cancer cells, reminiscent of transforming growth factor beta (TGFbeta) function and epithelial-to-mesenchymal transition. Indeed, inhibition of PDEF expression triggers a transcriptional program of genes involved in the TGFbeta pathway, migration, invasion, adhesion, and epithelial dedifferentiation. Our results establish PDEF as a critical regulator of genes involved in cell motility, invasion, and adhesion of prostate cancer cells.
authors.affiliation: BIDMC Genomics Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Gu
authors.forename: Luiz F
authors.initials: LF
authors.lastname: Zerbini
authors.forename: Hasan H
authors.initials: HH
authors.lastname: Otu
authors.forename: Manoj
authors.initials: M
authors.lastname: Bhasin
authors.forename: Quanli
authors.initials: Q
authors.lastname: Yang
authors.forename: Marie G
authors.initials: MG
authors.lastname: Joseph
authors.forename: Franck
authors.initials: F
authors.lastname: Grall
authors.forename: Tomi
authors.initials: T
authors.lastname: Onatunde
authors.forename: Ricardo G
authors.initials: RG
authors.lastname: Correa
authors.forename: Towia A
authors.initials: TA
authors.lastname: Libermann
mesh_terms: D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008648:Mesoderm / Q000473:pathology; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D050783:Proto-Oncogene Proteins c-ets / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D016023:Integrins; D050783:Proto-Oncogene Proteins c-ets; D034741:RNA, Small Interfering; C403974:SPDEF protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A