Stromal growth and epithelial cell proliferation in ventral prostates of liver X receptor knockout mice.
With specific liver X receptor alpha and beta (LXRalpha and LXRbeta) antibodies, we found that LXRalpha is strongly expressed in the luminal and basal cells of prostatic epithelium. The ventral prostates (VP) of LXRalpha(-/-) mice are characterized by the presence of smooth-muscle actin-positive stromal overgrowth around the prostatic ducts and by numerous fibrous nodules pushing into the ducts and causing obstruction, so that most of the ducts were extremely dilated. BrdU labeling and Ki67 staining revealed epithelial and stromal proliferation in the fibrous nodules. However, the dense stroma surrounding the ducts was not positive for proliferation markers. There was no detectable difference between WT and LXRalpha(-/-) mice VP in the expression of the androgen receptor, but there was an increase in nuclear expression of Snail and Smad 2/3, indicating enhanced TGF-beta signaling. Upon treatment of WT mice for 3 months with the LXR agonist T2320 or for 3 weeks with beta-sitosterol, LXRalpha was downregulated, and a VP phenotype similar to that of LXRalpha(-/-) mice resulted. We conclude that in rodents, LXRalpha seems to control VP stromal growth and that LXRalpha(-/-) mice may be a useful model to study prostatic stromal hyperplasia. Because LXRalpha is expressed in the epithelium, the excessive stromal growth in LXRalpha(-/-) mice indicates that LXRalpha is essential for epithelial stromal communication.
Kim
Hyun-Jin
HJ
Department of Biosciences and Nutrition, Karolinska Institutet, Novum S-14186, Sweden.
Andersson
Leif C
LC
Bouton
Didier
D
Warner
Margaret
M
Gustafsson
Jan-Ake
JA
D000818:Animals; D002450:Cell Communication; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000172:deficiency*; D004847:Epithelial Cells / Q000166:cytology*; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D057093:Orphan Nuclear Receptors; D011467:Prostate / Q000166:cytology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency*; D051899:Smad2 Protein / Q000235:genetics; D051900:Smad3 Protein / Q000235:genetics; D000071250:Snail Family Transcription Factors; D017154:Stromal Cells / Q000166:cytology*; D014157:Transcription Factors / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta