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Nkx3-1  -  NK-3 transcription factor, locus 1...

Mus musculus

Synonyms: Bax, Homeobox protein NK-3 homolog A, Homeobox protein Nkx-3.1, NKX3.1, NKX3A, ...
 
 
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Disease relevance of Nkx3-1

 

High impact information on Nkx3-1

  • Because human NKX3.1 is known to map to a prostate cancer hot spot, we propose that NKX3.1 is a prostate-specific tumor suppressor gene and that loss of a single allele may predispose to prostate carcinogenesis [3].
  • Here we show that the murine Nkx3.1 homeobox gene is the earliest known marker of prostate epithelium during embryogenesis and is subsequently expressed at all stages of prostate differentiation in vivo as well as in tissue recombinants [3].
  • A null mutation for Nkx3.1 obtained by targeted gene disruption results in defects in prostate ductal morphogenesis and secretory protein production [3].
  • Our findings underscore the significance of interactions between tissue-specific regulators such as Nkx3.1 and broad-spectrum tumor suppressors such as Pten in contributing to the distinct phenotypes of different cancers [5].
  • In this work, we elucidate how BMP signaling modulates the transcriptional repressor activity of Nkx3 [6].
 

Chemical compound and disease context of Nkx3-1

 

Biological context of Nkx3-1

  • Homozygous mutant mice for Nkx3.1 were viable and fertile, and the phenotype was, unexpectedly, confined to the prostate and palatine glands [8].
  • A murine homolog of bagpipe, Bax/Nkx3.1, is expressed in somites, blood vessels, and the male reproductive system during embryogenesis (this study), suggesting that this gene's function may be relevant for the development of these organs [9].
  • Interestingly, Nkx3.1 mapped to the central region of the mouse chromosome 14 and was linked to Nkx2.6, a murine homolog of Drosophila tinman [8].
  • Here, we investigated the role of the axial structures in the mediolateral patterning of the somite by using a newly identified murine homeobox gene, Nkx-3.1, as a medial somitic marker in explant in vitro assays [10].
  • Targeted disruption of the Nkx3.1 gene in mice results in morphogenetic defects of minor salivary glands: parallels to glandular duct morphogenesis in prostate [11].
 

Anatomical context of Nkx3-1

  • Nkx3.1 is an early marker of the sclerotome and a subset of vascular smooth muscle cells, and at later stages, this gene is expressed in the prostate, palatine glands, kidney, and restricted regions of the central nervous system [8].
  • Our results suggest that Nkx3.1 plays a unique role in regulating proliferation of glandular epithelium and in the formation of ducts in prostate and minor salivary glands [11].
  • Shh could induce and maintain Nkx-3.1 expression in pre-somitic mesoderm and young somites but not in more mature, differentiated ones [10].
  • The genetic locus of Nkx3.1, an early murine marker of sclerotome and prostate development, was disrupted by a knock in of CRE recombinase via homologous recombination in embryonic stem cells [12].
  • We found that the expression of Nkx-3.1 in pre-somitic tissue explants is induced by the notochord and maintained in newly-differentiated somites by the notochord and both ventral and dorsal parts of the neural tube [10].
 

Associations of Nkx3-1 with chemical compounds

  • Finally, we observe androgen independence of high-grade PIN lesions after androgen ablation of Nkx3.1(+/-); Pten(+/-) mice [13].
  • NKX3.1 binding to Topo I occurred independently of the Topo I NH2-terminal domain [14].
 

Regulatory relationships of Nkx3-1

 

Other interactions of Nkx3-1

 

Analytical, diagnostic and therapeutic context of Nkx3-1

References

  1. Emergence of androgen independence at early stages of prostate cancer progression in nkx3.1; pten mice. Gao, H., Ouyang, X., Banach-Petrosky, W.A., Shen, M.M., Abate-Shen, C. Cancer Res. (2006) [Pubmed]
  2. Vitamin d inhibits the formation of prostatic intraepithelial neoplasia in nkx3.1; pten mutant mice. Banach-Petrosky, W., Ouyang, X., Gao, H., Nader, K., Ji, Y., Suh, N., Dipaola, R.S., Abate-Shen, C. Clin. Cancer Res. (2006) [Pubmed]
  3. Roles for Nkx3.1 in prostate development and cancer. Bhatia-Gaur, R., Donjacour, A.A., Sciavolino, P.J., Kim, M., Desai, N., Young, P., Norton, C.R., Gridley, T., Cardiff, R.D., Cunha, G.R., Abate-Shen, C., Shen, M.M. Genes Dev. (1999) [Pubmed]
  4. Conditional loss of Nkx3.1 in adult mice induces prostatic intraepithelial neoplasia. Abdulkadir, S.A., Magee, J.A., Peters, T.J., Kaleem, Z., Naughton, C.K., Humphrey, P.A., Milbrandt, J. Mol. Cell. Biol. (2002) [Pubmed]
  5. Cooperativity of Nkx3.1 and Pten loss of function in a mouse model of prostate carcinogenesis. Kim, M.J., Cardiff, R.D., Desai, N., Banach-Petrosky, W.A., Parsons, R., Shen, M.M., Abate-Shen, C. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  6. Smad-dependent recruitment of a histone deacetylase/Sin3A complex modulates the bone morphogenetic protein-dependent transcriptional repressor activity of Nkx3.2. Kim, D.W., Lassar, A.B. Mol. Cell. Biol. (2003) [Pubmed]
  7. Haploinsufficiency at the Nkx3.1 locus. A paradigm for stochastic, dosage-sensitive gene regulation during tumor initiation. Magee, J.A., Abdulkadir, S.A., Milbrandt, J. Cancer Cell (2003) [Pubmed]
  8. Nkx3.1, a murine homolog of Ddrosophila bagpipe, regulates epithelial ductal branching and proliferation of the prostate and palatine glands. Tanaka, M., Komuro, I., Inagaki, H., Jenkins, N.A., Copeland, N.G., Izumo, S. Dev. Dyn. (2000) [Pubmed]
  9. Vertebrate homologs of tinman and bagpipe: roles of the homeobox genes in cardiovascular development. Tanaka, M., Kasahara, H., Bartunkova, S., Schinke, M., Komuro, I., Inagaki, H., Lee, Y., Lyons, G.E., Izumo, S. Dev. Genet. (1998) [Pubmed]
  10. Mediolateral patterning of somites: multiple axial signals, including Sonic hedgehog, regulate Nkx-3.1 expression. Kos, L., Chiang, C., Mahon, K.A. Mech. Dev. (1998) [Pubmed]
  11. Targeted disruption of the Nkx3.1 gene in mice results in morphogenetic defects of minor salivary glands: parallels to glandular duct morphogenesis in prostate. Schneider, A., Brand, T., Zweigerdt, R., Arnold, H. Mech. Dev. (2000) [Pubmed]
  12. Expression of an Nkx3.1-CRE gene using ROSA26 reporter mice. Stanfel, M.N., Moses, K.A., Carson, J.A., Zimmer, D.B., Demayo, F., Schwartz, R.J., Zimmer, W.E. Genesis (2006) [Pubmed]
  13. Nkx3.1; Pten mutant mice develop invasive prostate adenocarcinoma and lymph node metastases. Abate-Shen, C., Banach-Petrosky, W.A., Sun, X., Economides, K.D., Desai, N., Gregg, J.P., Borowsky, A.D., Cardiff, R.D., Shen, M.M. Cancer Res. (2003) [Pubmed]
  14. 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]
  15. Tissue-specific expression of murine Nkx3.1 in the male urogenital system. Sciavolino, P.J., Abrams, E.W., Yang, L., Austenberg, L.P., Shen, M.M., Abate-Shen, C. Dev. Dyn. (1997) [Pubmed]
  16. Transcription factors Nkx3.1 and Nkx3.2 (Bapx1) play an overlapping role in sclerotomal development of the mouse. Herbrand, H., Pabst, O., Hill, R., Arnold, H.H. Mech. Dev. (2002) [Pubmed]
  17. Interaction of Nkx3.1 and p27kip1 in prostate tumor initiation. Gary, B., Azuero, R., Mohanty, G.S., Bell, W.C., Eltoum, I.E., Abdulkadir, S.A. Am. J. Pathol. (2004) [Pubmed]
  18. Nkx3.1 mutant mice recapitulate early stages of prostate carcinogenesis. Kim, M.J., Bhatia-Gaur, R., Banach-Petrosky, W.A., Desai, N., Wang, Y., Hayward, S.W., Cunha, G.R., Cardiff, R.D., Shen, M.M., Abate-Shen, C. Cancer Res. (2002) [Pubmed]
 
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