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Gene Review

NKX3-1  -  NK3 homeobox 1

Homo sapiens

Synonyms: BAPX2, Homeobox protein NK-3 homolog A, Homeobox protein Nkx-3.1, NKX3, NKX3.1, ...
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Disease relevance of NKX3-1

  • We demonstrate that PTEN loss causes reduced NKX3.1 expression in both murine and human prostate cancers [1].
  • In 12 cases that also had high-grade prostatic intraepithelial neoplasia, NKX3.1 expression levels were similar in preinvasive and invasive cancer cells and significantly lower than adjacent normal cells [2].
  • Single-strand conformational polymorphism analysis of 48 radical prostatectomy cancer specimens and 3 metastases for the entire coding region of NKX3.1 showed no tumor-specific sequence alterations in 50 specimens and total absence of the gene in 1 specimen known to have a biallelic deletion of 8p21 [3].
  • Here we show that NKX3.1 expression is dramatically down-regulated in testicular cancer of germ cell origin [4].
  • Immunohistochemical analysis on a tissue microarray containing 510 testicular tissue samples indicate that NKX3.1 is expressed at high levels in normal germ cells and in carcinoma in situ, but is sharply decreased or absent in most seminomas and all embryonal carcinomas [4].

High impact information on NKX3-1


Chemical compound and disease context of NKX3-1


Biological context of NKX3-1


Anatomical context of NKX3-1


Associations of NKX3-1 with chemical compounds


Physical interactions of NKX3-1

  • Using NMR spectroscopy, three conserved motifs in a construct containing the N-terminal region and homeodomain of NKX3.1 were observed to interact with the MADS box domain of SRF [17].

Regulatory relationships of NKX3-1

  • Our results provide biochemical and cellular biologic evidence that NKX3.1 is down-regulated by p53 over-expression in prostate cancer cells [18].
  • NKX3.1 is an androgen-regulated prostate-specific homeobox gene that is thought to play an important role in prostate development and cancerogenesis [19].

Other interactions of NKX3-1


Analytical, diagnostic and therapeutic context of NKX3-1


  1. NKX3.1 stabilizes p53, inhibits AKT activation, and blocks prostate cancer initiation caused by PTEN loss. Lei, Q., Jiao, J., Xin, L., Chang, C.J., Wang, S., Gao, J., Gleave, M.E., Witte, O.N., Liu, X., Wu, H. Cancer Cell (2006) [Pubmed]
  2. Deletion, methylation, and expression of the NKX3.1 suppressor gene in primary human prostate cancer. Asatiani, E., Huang, W.X., Wang, A., Rodriguez Ortner, E., Cavalli, L.R., Haddad, B.R., Gelmann, E.P. Cancer Res. (2005) [Pubmed]
  3. Coding region of NKX3.1, a prostate-specific homeobox gene on 8p21, is not mutated in human prostate cancers. Voeller, H.J., Augustus, M., Madike, V., Bova, G.S., Carter, K.C., Gelmann, E.P. Cancer Res. (1997) [Pubmed]
  4. NKX3.1 expression is lost in testicular germ cell tumors. Skotheim, R.I., Korkmaz, K.S., Klokk, T.I., Abeler, V.M., Korkmaz, C.G., Nesland, J.M., Fosså, S.D., Lothe, R.A., Saatcioglu, F. Am. J. Pathol. (2003) [Pubmed]
  5. NKX3.1 is regulated by protein kinase CK2 in prostate tumor cells. Li, X., Guan, B., Maghami, S., Bieberich, C.J. Mol. Cell. Biol. (2006) [Pubmed]
  6. NKX3.1 homeodomain protein binds to topoisomerase I and enhances its activity. Bowen, C., Stuart, A., Ju, J.H., Tuan, J., Blonder, J., Conrads, T.P., Veenstra, T.D., Gelmann, E.P. Cancer Res. (2007) [Pubmed]
  7. Germ-line mutation of NKX3.1 cosegregates with hereditary prostate cancer and alters the homeodomain structure and function. Zheng, S.L., Ju, J.H., Chang, B.L., Ortner, E., Sun, J., Isaacs, S.D., Sun, J., Wiley, K.E., Liu, W., Zemedkun, M., Walsh, P.C., Ferretti, J., Gruschus, J., Isaacs, W.B., Gelmann, E.P., Xu, J. Cancer Res. (2006) [Pubmed]
  8. Full-length cDNA sequence and genomic organization of human NKX3A - alternative forms and regulation by both androgens and estrogens. Korkmaz, K.S., Korkmaz, C.G., Ragnhildstveit, E., Kizildag, S., Pretlow, T.G., Saatcioglu, F. Gene (2000) [Pubmed]
  9. Effects of 9-cis retinoic acid on human homeobox gene NKX3.1 expression in prostate cancer cell line LNCaP. Jiang, A.L., Zhang, P.J., Chen, W.W., Liu, W.W., Yu, C.X., Hu, X.Y., Zhang, X.Q., Zhang, J.Y. Asian J. Androl. (2006) [Pubmed]
  10. The corepressors silencing mediator of retinoid and thyroid hormone receptor and nuclear receptor corepressor are involved in agonist- and antagonist-regulated transcription by androgen receptor. Yoon, H.G., Wong, J. Mol. Endocrinol. (2006) [Pubmed]
  11. Loss of NKX3.1 expression in human prostate cancers correlates with tumor progression. Bowen, C., Bubendorf, L., Voeller, H.J., Slack, R., Willi, N., Sauter, G., Gasser, T.C., Koivisto, P., Lack, E.E., Kononen, J., Kallioniemi, O.P., Gelmann, E.P. Cancer Res. (2000) [Pubmed]
  12. A novel human prostate-specific, androgen-regulated homeobox gene (NKX3.1) that maps to 8p21, a region frequently deleted in prostate cancer. He, W.W., Sciavolino, P.J., Wing, J., Augustus, M., Hudson, P., Meissner, P.S., Curtis, R.T., Shell, B.K., Bostwick, D.G., Tindall, D.J., Gelmann, E.P., Abate-Shen, C., Carter, K.C. Genomics (1997) [Pubmed]
  13. The smooth muscle gamma-actin gene promoter is a molecular target for the mouse bagpipe homologue, mNkx3-1, and serum response factor. Carson, J.A., Fillmore, R.A., Schwartz, R.J., Zimmer, W.E. J. Biol. Chem. (2000) [Pubmed]
  14. Androgen regulation of prostate morphoregulatory gene expression: Fgf10-dependent and -independent pathways. Pu, Y., Huang, L., Birch, L., Prins, G.S. Endocrinology (2007) [Pubmed]
  15. Occurrence of NKX3.1 C154T polymorphism in men with and without prostate cancer and studies of its effect on protein function. Gelmann, E.P., Steadman, D.J., Ma, J., Ahronovitz, N., Voeller, H.J., Swope, S., Abbaszadegan, M., Brown, K.M., Strand, K., Hayes, R.B., Stampfer, M.J. Cancer Res. (2002) [Pubmed]
  16. DNA-binding sequence of the human prostate-specific homeodomain protein NKX3.1. Steadman, D.J., Giuffrida, D., Gelmann, E.P. Nucleic Acids Res. (2000) [Pubmed]
  17. Physical and functional interactions between the prostate suppressor homeoprotein NKX3.1 and serum response factor. Ju, J.H., Maeng, J.S., Zemedkun, M., Ahronovitz, N., Mack, J.W., Ferretti, J.A., Gelmann, E.P., Gruschus, J.M. J. Mol. Biol. (2006) [Pubmed]
  18. p53 overexpression represses androgen-mediated induction of NKX3.1 in a prostate cancer cell line. Jiang, A., Yu, C., Zhang, P., Chen, W., Liu, W., Hu, X., Zhang, J. Exp. Mol. Med. (2006) [Pubmed]
  19. Up-regulation of NKX3.1 expression and inhibition of LNCaP cell proliferation induced by an inhibitory element decoy. Jiang, A.L., Hu, X.Y., Zhang, P.J., He, M.L., Kong, F., Liu, Z.F., Yuan, H.Q., Zhang, J.Y. Acta Biochim. Biophys. Sin. (Shanghai) (2005) [Pubmed]
  20. 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]
  21. Gum mastic inhibits the expression and function of the androgen receptor in prostate cancer cells. He, M.L., Yuan, H.Q., Jiang, A.L., Gong, A.Y., Chen, W.W., Zhang, P.J., Young, C.Y., Zhang, J.Y. Cancer (2006) [Pubmed]
  22. The role of estrogens in normal and abnormal development of the prostate gland. Prins, G.S., Huang, L., Birch, L., Pu, Y. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
  23. Analysis of androgen regulated homeobox gene NKX3.1 during prostate carcinogenesis. Korkmaz, C.G., Korkmaz, K.S., Manola, J., Xi, Z., Risberg, B., Danielsen, H., Kung, J., Sellers, W.R., Loda, M., Saatcioglu, F. J. Urol. (2004) [Pubmed]
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