Loss of Nkx3.1 expression in bacterial prostatitis: a potential link between inflammation and neoplasia.
NKX3.1 is a homeodomain protein that functions as a dosage sensitive prostate-specific transcription factor. Diminished NKX3.1 expression is associated with prostate epithelial cell proliferation in vitro and with increasing Gleason grade in patient samples. Mouse Nkx3.1 also functions as a negative regulator of prostate cell growth in prostate cancer models. Identifying biological and environmental factors that modulate NKX3.1 accumulation is therefore central to efforts aimed at elucidating prostate growth control mechanisms. To determine the effect of inflammation on Nxk3.1 accumulation, bacterial prostatitis was induced by intraurethral inoculation of a uropathogenic E. coli strain in mice. Nkx3.1 expression was profoundly reduced in infected prostate lobes and correlated with increased expression of a proliferation marker. Androgen receptor levels were also reduced in concert with Nkx3.1, and a marked increase in the basal cell marker p63 was observed. Analyses of the inflammatory infiltrate revealed a classic acute inflammatory response that attained characteristics of a chronic state within fourteen days postinoculation. Comparison of the four prostate lobes revealed clear differences in the extent of inflammation. These data demonstrate that acute inflammation in response to a bacterial agent in the prostate is associated with a significant diminution in the level of a key regulator of prostate cell proliferation. These observations provide a plausible mechanism whereby prostate inflammation may establish a local environment conducive to epithelial cell growth.
Khalili
May
M
Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD 21250, USA.
Mutton
Laura N
LN
Gurel
Bora
B
Hicks
Jessica L
JL
De Marzo
Angelo M
AM
Bieberich
Charles J
CJ
D000818:Animals; D049109:Cell Proliferation; D004926:Escherichia coli / Q000378:metabolism; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D007249:Inflammation; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018384:Oxidative Stress; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011472:Prostatitis / Q000150:complications* / Q000382:microbiology* / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis*
D018398:Homeodomain Proteins; C491178:NKX3-1 protein, human; D014157:Transcription Factors