RUNX1 (AML-1) and RUNX2 (AML-3) cooperate with prostate-derived Ets factor to activate transcription from the PSA upstream regulatory region.
The RUNX transcription factors (RUNX1, RUNX2, and RUNX3) play essential roles in hematopoiesis and skeletal development. Consistent with these roles in differentiation and cell cycle, the activity of both RUNX1 and RUNX3 is perturbed in cancer. To determine a role for the RUNX factors in prostate biology, we investigated the expression of RUNX factors in prostate epithelial cell lines and normal prostate tissue. RUNX1, RUNX2, and RUNX3 were expressed in both normal prostate tissue and an immortalized, non-transformed cell line. We found that prostate cancer-derived cell lines expressed RUNX1 and RUNX2, but not RUNX3. Next, we sought to identify prostate-specific genes whose expression could be regulated by RUNX proteins. Four consensus RUNX sites are located within the prostate-specific antigen (PSA) regulatory region. Chromatin immunoprecipitation (ChIP) analysis showed that RUNX1 is specifically bound to the PSA regulatory region in LNCaP cells. RUNX1 and RUNX2 activated the PSA regulatory region alone or cooperatively with prostate-derived ETS factor (PDEF) and RUNX1 physically associated with PDEF. Taken together, our results suggest that RUNX factors participate in prostate epithelial cell function and cooperate with an Ets transcription factor to regulate PSA gene expression.
Fowler
Marcie
M
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 711130, USA.
Borazanci
Erkut
E
McGhee
Laura
L
Pylant
Shannon Walls
SW
Williams
B Jill
BJ
Glass
Jonathan
J
Davis
J Nathan
JN
Meyers
Shari
S
D001483:Base Sequence; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism / Q000502:physiology*; D050677:Core Binding Factor Alpha 3 Subunit / Q000378:metabolism / Q000502:physiology*; D017931:DNA Primers; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008297:Male; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D017430:Prostate-Specific Antigen / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets / Q000378:metabolism / Q000502:physiology*; D012045:Regulatory Sequences, Nucleic Acid; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000502:physiology*
D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D017931:DNA Primers; D050783:Proto-Oncogene Proteins c-ets; C493728:RUNX1 protein, human; C493729:Runx3 protein, human; C403974:SPDEF protein, human; D017430:Prostate-Specific Antigen