PMID:10625666

Citation	Oettgen, P, Finger, E, Sun, Z, Akbarali, Y, Thamrongsak, U, Boltax, J, Grall, F, Dube, A, Weiss, A, Brown, L, Quinn, G, Kas, K, Endress, G, Kunsch, C and Libermann, TA (2000) PDEF, a novel prostate epithelium-specific ets transcription factor, interacts with the androgen receptor and activates prostate-specific antigen gene expression. J. Biol. Chem. 275:1216-25
Abstract	Prostate cancer, the most frequent solid cancer in older men, is a leading cause of cancer deaths. Although proliferation and differentiation of normal prostate epithelia and the initial growth of prostate cancer cells are androgen-dependent, prostate cancers ultimately become androgen-independent and refractory to hormone therapy. The prostate-specific antigen (PSA) gene has been widely used as a diagnostic indicator for androgen-dependent and -independent prostate cancer. Androgen-induced and prostate epithelium-specific PSA expression is regulated by a proximal promoter and an upstream enhancer via several androgen receptor binding sites. However, little progress has been made in identifying androgen-independent regulatory elements involved in PSA gene regulation. We report the isolation of a novel, prostate epithelium-specific Ets transcription factor, PDEF (prostate-derived Ets factor), that among the Ets family uniquely prefers binding to a GGAT rather than a GGAA core. PDEF acts as an androgen-independent transcriptional activator of the PSA promoter. PDEF also directly interacts with the DNA binding domain of androgen receptor and enhances androgen-mediated activation of the PSA promoter. Our results, as well as the critical roles of other Ets factors in cellular differentiation and tumorigenesis, strongly suggest that PDEF is an important regulator of prostate gland and/or prostate cancer development.
Links	PubMed
Keywords	Amino Acid Sequence; Base Sequence; Binding Sites; Cell Line; Cells, Cultured; Gene Expression Regulation; Humans; Keratinocytes; Male; Molecular Sequence Data; Promoter Regions, Genetic; Prostate/metabolism; Prostate-Specific Antigen/genetics; Proto-Oncogene Proteins/chemistry; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-ets; Recombinant Proteins/metabolism; Sequence Alignment; Sequence Homology, Amino Acid; Transcription Factors/chemistry; Transcription Factors/genetics; Transcription Factors/metabolism; Transcriptional Activation; Tumor Cells, Cultured
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:SPDEF	involved_in	GO:0007275: multicellular organism development	ECO:0000304: author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete

References

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