Pdef expression in human breast cancer is correlated with invasive potential and altered gene expression.
Ets transcription factors control multiple biological processes, including cell proliferation, differentiation, apoptosis, angiogenesis, transformation, and invasion. Pdef is an Ets transcription factor originally identified in prostate tissue. We demonstrate that human Pdef is expressed at high levels primarily in tissues with high epithelial cell content, including prostate, colon, and breast. We also determined that Pdef protein is reduced in human invasive breast cancer and is absent in invasive breast cancer cell lines. We next assessed the functional consequences of these observations. Significantly, expression of Pdef in breast cancer cells leads to inhibition of invasion, migration, and growth. Expression of Pdef also results in the down-regulation of urokinase-type plasminogen activator and activation of the promoter of the tumor suppressor gene, MASPIN: Growth-suppressive effects of Pdef expression are mediated in part by a G(0)-G(1) cell cycle arrest associated with elevated p21 levels. Collectively, these results indicate that Pdef loss may alter the expression of genes controlling progression to invasive breast cancer.
Feldman
Ron J
RJ
Laboratory of Cancer Genomics, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.
Sementchenko
Victor I
VI
Gayed
Maged
M
Fraig
Mostafa M
MM
Watson
Dennis K
DK
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D009361:Neoplasm Invasiveness; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D014407:Tumor Cells, Cultured
D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; C403974:SPDEF protein, human; D014157:Transcription Factors