Reduced PDEF expression increases invasion and expression of mesenchymal genes in prostate cancer cells.
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.
Gu
Xuesong
X
BIDMC Genomics Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.
Zerbini
Luiz F
LF
Otu
Hasan H
HH
Bhasin
Manoj
M
Yang
Quanli
Q
Joseph
Marie G
MG
Grall
Franck
F
Onatunde
Tomi
T
Correa
Ricardo G
RG
Libermann
Towia A
TA
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
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