Ets-1 is implicated in the regulation of androgen co-regulator FHL2 and reveals specificity for migration, but not invasion, of PC3 prostate cancer cells.
Different members of the Ets-family of transcription factors are involved in TMPRSS-2-Ets translocations frequently found in human prostate cancers. We previously reported that Ets-1, which is the prototype of Ets-family members, promotes both migration and invasion of melanoma, Hela and glioma cells. Here, we examined whether Ets-1 has a similar effect upon migration and invasion of PC3 prostate cancer cells, and whether it is implicated in the regulation of the androgen co-regulator four and a half LIM only protein-2 (FHL2). Two stable PC3 cell cultures were established by transfection with either an Ets-1 inverse antisense expression vector or a mock control vector. Western blot analysis confirmed presence of Ets-1 in mock and absence in Ets-1 inverse cells. Microarray and qRT-PCR revealed an up-regulation of FHL2 in Ets-1 blocked cells, compared to mock. To examine the effects of Ets-1 upon cell migration, a wound assay was performed, and demonstrated that wounds were completely colonized by mock compared to Ets-1 blocked cells after 55 h. Evaluation of the effect upon invasion was examined using the Boyden chamber, which revealed no significant difference between mock and Ets-1 blocked cells. In conclusion, our study demonstrated for the first time that Ets-1 is implicated in the regulation of the androgen co-regulator FHL2, and reveals specificity of action for migration, but not invasion of PC3 prostate cancer cells.
Institute of Pathology, University Hospital Bonn, 53127 Bonn, Germany.
David
D
Adler
Berit
B
Langer
Andreas
A
Lindstrot
Alexandra
A
Florin
Anja
A
Bosserhoff
Reinhard
R
Buettner
Nicolas
N
Wernert
D000728:Androgens / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D060850:LIM-Homeodomain Proteins; D008297:Male; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D014945:Wound Healing
D000728:Androgens; D014408:Biomarkers, Tumor; C494041:ETS1 protein, human; C105987:FHL2 protein, human; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D050784:Proto-Oncogene Protein c-ets-1; D012333:RNA, Messenger; D014157:Transcription Factors