Loss of NKX3.1 expression in human prostate cancers correlates with tumor progression

Cancer Res. 2000 Nov 1;60(21):6111-5.


NKX3.1 is a prostate-specific homeobox gene located on chromosome 8p21. In the mouse, Nkx3.1 has growth-suppressive and differentiating effects on prostatic epithelium. Mutations of the coding region of NKX3.1 were not found in human prostate cancer, failing to support the notion that NKX3.1 was a tumor suppressor gene. To study the expression o NKX3.1 protein in human tissues and prostate cancer, we derived a rabbit antiserum against purified recombinant NKX3.1. Among normal human tissues, NKX3.1 expression was seen in testis, in rare pulmonary mucous glands, and in isolated regions of transitional epithelium of the ureter. NKX3.1 was uniformly expressed in nuclei of normal prostate epithelial cells in 61 histological sections from radical prostatectomy specimens. We analyzed 507 samples of neoplastic prostate epithelium, most of which were contained on a tissue microarray that contained samples from different stages of prostatic neoplasia. We observed complete loss of NKX3.1 expression in 5% of benign prostatic hyperplasias, 20% of high-grade prostatic intraepithelial neoplasias, 6% of T1a/b samples, 22% of T3/4 samples, 34% of hormone-refractory prostate cancers, and 78% of metastases. Our data show that NKX3.1 expression is highly, but not exclusively, specific for the prostate. Loss of NKX3.1 expression is strongly associated with hormone-refractory disease and advanced tumor stage in prostate cancer (P < 0.0001).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Disease Progression
  • Epithelium / metabolism
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing*
  • Genes, Tumor Suppressor
  • Homeodomain Proteins / biosynthesis
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / immunology
  • Humans
  • Immune Sera
  • Immunohistochemistry
  • Male
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rabbits
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / isolation & purification
  • Testis / metabolism
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics*
  • Transcription Factors / immunology


  • Homeodomain Proteins
  • Immune Sera
  • NKX3-1 protein, human
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Transcription Factors