Expression of Foxa transcription factors in the developing and adult murine prostate.
BACKGROUND
The Foxa family (a1, a2, and a3) of proteins are transcription factors that are central to endodermal development. Recently, Foxa1 has been shown to regulate the transcription of several murine and human prostate specific genes involved in differentiated function by interacting with DNA promoter sequences and androgen receptors. Currently, the developmental expression pattern of Foxa proteins in the murine prostate is unknown.


METHODS
Male CD-1 mice (embryonic, prepubertal, pubertal, and adult) were used for immunohistochemical analysis of Foxa1, a2, and a3. Immunofluorescence was also performed for androgen receptor and cytokeratin 14 expression. Prostate tissue from pre-pubertal, pubertal, and adult mice were analyzed by Western blot and RT-PCR analysis for Foxa1, a2, and a3 expression.


RESULTS
Strong Foxa1 immunoreactivity was observed in epithelial cells throughout prostate development, growth, and adult differentiation. Prominent Foxa2 protein expression was only observed in the early stages of prostate development and was exclusively localized to epithelial cells of the forming buds. RT-PCR analysis identified low Foxa2 mRNA expression levels in the ventral and dorsolateral lobes of the adult prostate, with Foxa2 epithelial cell expression being localized to periurethral regions of the murine adult prostatic complex. Foxa3 expression was not observed in the murine prostate.


CONCLUSIONS
Foxa proteins represent epithelial cell markers in the murine prostate gland. The early expression of Foxa1 and a2 proteins in prostate formation suggests that these proteins play an important role in normal prostate development, in addition to differentiated secretory function.
Mirosevich
Janni
J
Vanderbilt Prostate Cancer Center, Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2765, USA.
Gao
Nan
N
Matusik
Robert J
RJ
D000818:Animals; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004847:Epithelial Cells; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D051541:Hepatocyte Nuclear Factor 3-alpha; D051542:Hepatocyte Nuclear Factor 3-beta; D051543:Hepatocyte Nuclear Factor 3-gamma; D008297:Male; D051379:Mice; D009687:Nuclear Proteins / Q000096:biosynthesis*; D011467:Prostate / Q000254:growth & development*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis*
D004268:DNA-Binding Proteins; C496500:Foxa1 protein, mouse; C496503:Foxa2 protein, mouse; C496506:Foxa3 protein, mouse; D051541:Hepatocyte Nuclear Factor 3-alpha; D009687:Nuclear Proteins; D014157:Transcription Factors; D051543:Hepatocyte Nuclear Factor 3-gamma; D051542:Hepatocyte Nuclear Factor 3-beta