A comparison of prostatic development in xenografts of human fetal prostate and human female fetal proximal urethra grown in dihydrotestosterone-treated hosts

Copyright © 2020 International Society of Differentiation. Published by Elsevier B.V. All rights reserved..

The goal of this paper is to explore the ability of the human female urogenital sinus immediately below the bladder (proximal urethra) to undergo prostatic development in response to dihydrotestosterone (DHT). To establish this idea, xenografts of human fetal female proximal urethra were grown in castrated nude mouse hosts receiving a subcutaneous DHT pellet. To verify the prostatic nature of the resultant glands, DHT-treated human fetal female urethral xenografts were compared with human fetal prostatic xenografts (derived from male specimens) grown in untreated and DHT-treated castrated mouse hosts and human fetal female proximal urethral xenografts grown in untreated castrated hosts. The resultant glands observed in DHT-treated human fetal female proximal urethral xenografts expressed 3 prostate-specific markers, NKX3.1, prostate specific antigen and prostatic acid phosphatase as well as the androgen receptor. Glands induced by DHT exhibited a protein expression profile of additional immunohistochemical markers (seven keratins, RUNX1, ESR2, TP63 and FOXA1) consistent with the unique spatial pattern of these proteins in prostatic ducts. Xenografts of human fetal female proximal urethra grown in DHT-treated hosts also expressed one of the salient features of prostatic development, namely androgen responsiveness. The experimental induction of prostatic differentiation from human fetal female proximal urethra makes possible future in-depth analysis of the molecular pathways directly involved in initiation of human prostatic development and subsequent epithelial differentiation, and more important whether the molecular pathways involved in human prostatic development are similar/identical versus different from that in murine prostatic development.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:115

Enthalten in:

Differentiation; research in biological diversity - 115(2020) vom: 01. Sept., Seite 37-52

Sprache:

Englisch

Beteiligte Personen:

Cunha, Gerald R [VerfasserIn]
Cao, Mei [VerfasserIn]
Franco, Omar [VerfasserIn]
Baskin, Laurence S [VerfasserIn]

Links:

Volltext

Themen:

08J2K08A3Y
AR protein, human
Androgen receptor
Core Binding Factor Alpha 2 Subunit
Development
Dihydrotestosterone
EC 3.4.21.77
ESR2 protein, human
Estrogen Receptor beta
FOXA1 protein, human
Female prostate
Hepatocyte Nuclear Factor 3-alpha
Homeodomain Proteins
Journal Article
NKX3-1 protein, human
NKX3.1
Prostate-Specific Antigen
Receptors, Androgen
Research Support, N.I.H., Extramural
TP63 protein, human
Transcription Factors
Tumor Suppressor Proteins
Urethra

Anmerkungen:

Date Completed 13.08.2021

Date Revised 10.11.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.diff.2020.06.001

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM314342249