Tissue-specific expression of murineNkx3.1 in the male urogenital system

Sciavolino, Peter J.; Abrams, Elliott W.; Yang, Lu; Austenberg, Leif P.; Shen, Michael M.; Abate‐Shen, Cory

doi:10.1002/(sici)1097-0177(199705)209:1<127::aid-aja12>3.0.co;2-z

Cited by 157 publications

(101 citation statements)

References 40 publications

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“…Following neonatal exposure to high-dose estrogen, Hoxb13 expression was immediately and permanently suppressed in all prostate lobes with the most significant reduction (80%) observed in the ventral prostate gland. Another critical homeobox gene, the androgen-regulated Nkx3.1, is normally expressed in UGS-derived prostate epithelium where it plays a role in differentiation and growth (64,65). In control rats, a marked peak in Nkx3.1 expression was observed postnatally between days 6-15 of life which subsequently declined to steady-state levels thereafter.…”

Section: Molecular Pathways For Developmental Estrogenization Of the mentioning

confidence: 99%

Developmental estrogen exposures predispose to prostate carcinogenesis with aging☆

Prins

Birch

Tang

et al. 2007

Reproductive Toxicology

208

162

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Prostate morphogenesis occurs in utero in humans and during the perinatal period in rodents. While largely driven by androgens, there is compelling evidence for a permanent influence of estrogens on prostatic development. If estrogenic exposures are abnormally high during the critical developmental period, permanent alterations in prostate morphology and function are observed, a process referred to as developmental estrogenization. Using the neonatal rodent as an animal model, it has been shown that early exposure to high doses of estradiol results in an increased incidence of prostatic lesions with aging which include hyperplasia, inflammatory cell infiltration and prostatic intraepithelial neoplasia or PIN, believed to be the precursor lesion for prostatic adenocarcinoma. The present review summarizes research performed in our laboratory to characterize developmental estrogenization and identify the molecular pathways involved in mediating this response. Furthermore, recent studies performed with low-dose estradiol exposures during development as well as exposures to environmentally relevant doses of the endocrine disruptor bisphenol A show increased susceptibility to PIN lesions with aging following additional adult exposure to estradiol. Gene methylation analysis revealed a potential epigenetic basis for the estrogen imprinting of the prostate gland. Taken together, our results suggest that a full range of estrogenic exposures during the postnatal critical period -from environmentally relevant bisphenol A exposure to low-dose and pharmacologic estradiol exposures -results in an increased incidence and susceptibility to neoplastic transformation of the prostate gland in the aging male which may provide a fetal basis for this adult disease.

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Section: Molecular Pathways For Developmental Estrogenization Of the mentioning

confidence: 99%

Developmental estrogen exposures predispose to prostate carcinogenesis with aging☆

Prins

Birch

Tang

et al. 2007

Reproductive Toxicology

208

162

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“…Embryonic endoderm gives rise to the bladder urothelium while the connective tissues and smooth muscle of the developing bladder are derived from the peri-cloacal mesenchyme (Haraguchi et al, 2007;Brenner-Anantharam et al, 2007). Genetic studies indicate the homeobox genes play an important role in determining the global patterning of the urogenital system (Satokata et al, 1995;Sciavolino et al, 1997;Warot et al, 1997;Goodman and Scambler, 2001;de Santa and Roberts, 2002;Troy et al, 2003), while key signaling molecules like sonic hedgehog and wnts have been implicated in determining the regional patterning within specific urogenital organs (Perriton et al, 2002;Freestone et al, 2003;Mericskay et al, 2004). The differentiation program responsible for the development of smooth muscle involves the complex interaction of epigenetic and genetic events including chromatin remodeling and acetylation, the SRF-myocar-din pathway, basic helix-loop-helix factors, AP-1 complex genes, and the ternary complex factors of the ETS domain family (Manabe and Owens, 2001;Chen et al, 2002;Du et al, 2003;Kumar and Owens, 2003;Miano, 2003;Wang et al, 2003Wang et al, , 2004Yoshida et al, 2003;Buchwalter et al, 2004;Spin et al, 2004;McDonald et al, 2006;Pipes et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional profiling of the megabladder mouse: A unique model of bladder dysmorphogenesis

Singh¹,

Robinson²,

Ismail³

et al. 2007

Developmental Dynamics

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Recent studies in our lab identified a mutant mouse model of obstructive nephropathy designated mgb for megabladder. Homozygotic mgb mice (mgb؊/؊) develop lower urinary tract obstruction in utero due to a lack of bladder smooth muscle differentiation. This defect is the result of a random transgene insertion/translocation into chromosomes 11 and 16. Transcriptional profiling identified a significantly over-expressed cluster of gene products located on the translocated fragment of chromosome 16 including urotensin II-related peptide (Urp), which was shown to be preferentially over-expressed in developing mgb؊/؊ bladders. Pathway analysis of mgb microarray data indicated dysregulation of at least 60 gene products associated with smooth muscle development. In conclusion, the results of this study indicate that the molecular pathways controlling normal smooth muscle development are severely altered in mgb؊/؊ bladders, and provide the first evidence that Urp may play a critical role in bladder smooth muscle development. Developmental Dynamics 237:170 -186, 2008.

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“…Our work has focused on the Nkx3.1 homeobox gene because of its restricted expression in the prostate and essential role in prostate differentiation and function (6,7). Loss of function of Nkx3.1 in mice results in prostatic epithelial hyperplasia and dysplasia as a correlate of aging (7), and Nkx3.1 heterozygotes display a similar although less severe phenotype than homozygotes, indicating haploinsufficiency (7).…”

mentioning

confidence: 99%

Cooperativity of Nkx3.1 and Pten loss of function in a mouse model of prostate carcinogenesis

Kim

Cardiff

Desai

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Tissue-specific expression of murineNkx3.1 in the male urogenital system

Cited by 157 publications

References 40 publications

Developmental estrogen exposures predispose to prostate carcinogenesis with aging☆

Developmental estrogen exposures predispose to prostate carcinogenesis with aging☆

Transcriptional profiling of the megabladder mouse: A unique model of bladder dysmorphogenesis

Cooperativity of Nkx3.1 and Pten loss of function in a mouse model of prostate carcinogenesis

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