Accession Number:

ADA415376

Title:

NKX3.1 in Prostate Cancer

Descriptive Note:

Final rept. 1 Jul 1998-31 Dec 2002, Phase II

Corporate Author:

GEORGETOWN UNIV WASHINGTON DC

Personal Author(s):

Report Date:

2003-01-01

Pagination or Media Count:

86.0

Abstract:

NKX3.1 is a prostate-specific homeobox gene that undergoes loss of heterozygosity in -85 of prostate cancers, but one normal gene copy is retained in tumor cells. Haploinsuffiency of murine NKX3.1 is sufficient to permit prostatic hyperplasia and dysplasia later in life. Consistent with the findings in mouse models human NKX3.1 protein expression is substantially reduced in 80-90 of primary prostate cancer. Complete loss of NKX3.1 expression is seen mostly late in disease and in metastatic foci. Loss of NKX3.1 expression cannot be used as a prognostic marker in primary prostate cancer. Reduced expression of NKX3.1 in murine models and human prostate cancer occurs at the protein and not at the mRNA level. NKX3.1 promoter methylation is not a significant factor in reduced NKX3.1 expression in prostate cancer cell lines and tumors. In tumor model systems NKX3.1 has tumor suppressor properties and inhibits growth of human tumor cell xenografts in immunodeficient mice. NKX3.1 is therefore a candidate gatekeeper gene for human prostate cancer and an important focus of potential targeted therapies for prostate cancer.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE