Conditional Loss of Nkx3.1 in Adult Mice Induces Prostatic Intraepithelial Neoplasia

Abstract

The homeodomain-containing transcription factor NKX3.1 is a putative prostate tumor suppressor that is expressed in a largely prostate-specific and androgen-regulated manner. Loss of NKX3.1 protein expression is common in human prostate carcinomas and prostatic intraepithelial neoplasia (

Dual activities of galectin-3 in human prostate cancer: tumor suppression of nuclear galectin-3 vs tumor promotion of cytoplasmic galectin-3

“…Another member of the Nkx family, Nkx3.1, has been found in the nucleus (Bowen et al, 2000;Korkmaz et al, 2000) of both normal (Bieberich et al, 1996;Gelmann et al, 2003) and prostate cancer cells (Bowen et al, 2000;Gelmann et al, 2003), including the LNCaP cell line (Bowen et al, 2000). As Nkx3.1 is considered as a prostate tumor suppressor (Bhatia-Gaur et al, 1999;Bowen et al, 2000;Abdulkadir et al, 2002;Kim et al, 2002), we postulated that, in the nucleus, Gal-3 could decrease the expression of the cancer phenotype by interacting with Nkx3.1, but we were unable to demonstrate an interaction between these proteins by co-immunoprecipitation (data not shown). Anyhow, a deeper investigation of the nuclear components that interact with Gal-3 is necessary to understand better the mechanisms of action of nuclear Gal-3.…”

Microarray coupled to quantitative RT–PCR analysis of androgen-regulated genes in human LNCaP prostate cancer cells

“…The R1881 time-course cluster U2 (Figure 2), which represents genes whose expression is stimulated early after R1881 treatment and then falls by 48 h, included the androgen-regulated genes GREB1 (Rae et al, 2006) and NKX3-1 described earlier (Figure 6). The NKX3-1 homeobox gene is frequently deleted in prostate cancer and knockout mice are susceptible to prostatic intraepithelial neoplasia (Abdulkadir et al, 2002;Kim et al, 2002), indicating that NKX3-1 is a tumour suppressor gene in the prostate. NKX3-1 expression was stimulated 10-fold by R1881 and 3-7-fold by the other ligands ( Figure 5).…”

Decreased NKX3.1 Protein Expression in Focal Prostatic Atrophy, Prostatic Intraepithelial Neoplasia, and Adenocarcinoma: Association with Gleason Score and Chromosome 8p Deletion

“…Compound mutant mouse studies indicate that cooperativity exists between Nkx3.1 and the tumor suppressors Pten and Cdkn1b (encoding p27; refs. [13][14][15][16][17]. These compound mutants develop PIN lesions that progress to invasive carcinomas and at times to metastatic disease.…”