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Gene Review

SPDEF  -  SAM pointed domain containing ETS...

Homo sapiens

Synonyms: PDEF, PSE, Prostate epithelium-specific Ets transcription factor, Prostate-derived Ets factor, Prostate-specific Ets, ...


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Disease relevance of SPDEF

  • 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 [1].
  • High levels of prostate-derived Ets factor (PDEF) mRNA have been identified in breast cancer compared to normal breast [2].
  • RT-PCR expression analysis of PDEF showed it to be overexpressed in 14 of 20 primary human breast tumors and in one metastases tested [3].
  • These findings indicate that PDEF may be regulated by Erbb2 or EGFR-activated signaling pathways in breast cancer cells [4].

High impact information on SPDEF


Biological context of SPDEF

  • Cotransfection analyses demonstrated that NKX-3.1 can abolish the transcriptional activation function of PDEF on the prostate-specific antigen (PSA) promoter [7].
  • PDEF, a novel prostate epithelium-specific ets transcription factor, interacts with the androgen receptor and activates prostate-specific antigen gene expression [1].
  • Furthermore, cells coexpressing PDEF with either ErbB2 or CSF-1R/CSF-1 induced a dramatic invasive phenotype in three-dimensional cultures [6].
  • By comparing to the baseline construct, PSE, containing the PSA enhancer (-5322 to -2855) fused to the proximal promoter (-541 to +12), the three most efficacious chimeric constructs, PSE-BA (insertion of ARE4), PSE-BC (duplication of core) and PSE-BAC (insertion of core and ARE4), are 7.3-, 18.9-, and 9.4-fold higher, respectively [8].
  • Here we report a 2.0 A crystal structure of the PDEF Ets domain in complex with a natural, high-affinity DNA binding site in the promoter/enhancer region of the human prostate specific antigen gene [9].

Anatomical context of SPDEF


Associations of SPDEF with chemical compounds


Regulatory relationships of SPDEF

  • Here we show that PDEF stimulates the p62 promoter through at least two sites, and likely acts as a coactivator [2].
  • Furthermore, PDEF promoted anchorage-independent growth of ErbB2 and CSF-1R/CSF-1-expressing cells [6].

Other interactions of SPDEF


Analytical, diagnostic and therapeutic context of SPDEF


  1. PDEF, a novel prostate epithelium-specific ets transcription factor, interacts with the androgen receptor and activates prostate-specific antigen gene expression. 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., Libermann, T.A. J. Biol. Chem. (2000) [Pubmed]
  2. p62 overexpression in breast tumors and regulation by prostate-derived Ets factor in breast cancer cells. Thompson, H.G., Harris, J.W., Wold, B.J., Lin, F., Brody, J.P. Oncogene (2003) [Pubmed]
  3. Prostate epithelium-derived Ets transcription factor mRNA is overexpressed in human breast tumors and is a candidate breast tumor marker and a breast tumor antigen. Ghadersohi, A., Sood, A.K. Clin. Cancer Res. (2001) [Pubmed]
  4. Proteomic analysis of a PDEF Ets transcription factor-interacting protein complex. Cho, J.Y., Lee, M., Ahn, J.M., Park, E.S., Cho, J.H., Lee, S.J., Kim, B.G., Heo, S.H., Park, H.J., Zerbini, L.F., Hwang, D., Libermann, T.A. J. Proteome Res. (2009) [Pubmed]
  5. A common octamer motif binding protein is involved in the transcription of U6 snRNA by RNA polymerase III and U2 snRNA by RNA polymerase II. Carbon, P., Murgo, S., Ebel, J.P., Krol, A., Tebb, G., Mattaj, L.W. Cell (1987) [Pubmed]
  6. Novel role for PDEF in epithelial cell migration and invasion. Gunawardane, R.N., Sgroi, D.C., Wrobel, C.N., Koh, E., Daley, G.Q., Brugge, J.S. Cancer Res. (2005) [Pubmed]
  7. NKX-3.1 interacts with prostate-derived Ets factor and regulates the activity of the PSA promoter. Chen, H., Nandi, A.K., Li, X., Bieberich, C.J. Cancer Res. (2002) [Pubmed]
  8. Chimeric PSA enhancers exhibit augmented activity in prostate cancer gene therapy vectors. Wu, L., Matherly, J., Smallwood, A., Adams, J.Y., Billick, E., Belldegrun, A., Carey, M. Gene Ther. (2001) [Pubmed]
  9. Analysis of the 2.0 A crystal structure of the protein-DNA complex of the human PDEF Ets domain bound to the prostate specific antigen regulatory site. Wang, Y., Feng, L., Said, M., Balderman, S., Fayazi, Z., Liu, Y., Ghosh, D., Gulick, A.M. Biochemistry (2005) [Pubmed]
  10. Pdef expression in human breast cancer is correlated with invasive potential and altered gene expression. Feldman, R.J., Sementchenko, V.I., Gayed, M., Fraig, M.M., Watson, D.K. Cancer Res. (2003) [Pubmed]
  11. Prostate-Specific Ets (PSE) factor: a novel marker for detection of metastatic breast cancer in axillary lymph nodes. Mitas, M., Mikhitarian, K., Hoover, L., Lockett, M.A., Kelley, L., Hill, A., Gillanders, W.E., Cole, D.J. Br. J. Cancer (2002) [Pubmed]
  12. The proximal element is capable of determining proper temporal expression of the embryonic sea urchin U2 snRNA gene. Stefanovic, B., Marzluff, W.F. Gene Expr. (1994) [Pubmed]
  13. Silibinin down-regulates prostate epithelium-derived Ets transcription factor in LNCaP prostate cancer cells. Thelen, P., Jarry, H., Ringert, R.H., Wuttke, W. Planta Med. (2004) [Pubmed]
  14. Structural and functional analysis of domains mediating interaction between NKX-3.1 and PDEF. Chen, H., Bieberich, C.J. J. Cell. Biochem. (2005) [Pubmed]
  15. Cloning and expression of the mouse Pse gene encoding a novel Ets family member. Yamada, N., Tamai, Y., Miyamoto, H., Nozaki, M. Gene (2000) [Pubmed]
  16. Prostate-specific transcription factor hPSE is translated only in normal prostate epithelial cells. Nozawa, M., Yomogida, K., Kanno, N., Nonomura, N., Miki, T., Okuyama, A., Nishimune, Y., Nozaki, M. Cancer Res. (2000) [Pubmed]
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