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Title: | Aberrant expression and regulation of NR2F2 and CTNNB1 in uterine fibroids. | Authors: | Martelotto L.;Zaitseva M.;Waldrip L.;Nevzorova J.;Rogers P.A.W.;Vollenhoven B.J. ;Holdsworth-Carson S.J. | Monash Health Department(s): | Obstetrics and Gynaecology (Monash Women's) | Institution: | (Zaitseva, Holdsworth-Carson, Nevzorova, Rogers) Department of Obstetrics and Gynaecology, Royal Women's Hospital, University of Melbourne, 20 Flemington Road, Parkville, VIC 3052, Australia (Waldrip, Vollenhoven) Department of Obstetrics and Gynaecology, Monash Medical Centre, Monash University, 246 Clayton Road, Clayton, VIC 3168, Australia (Martelotto) Department of Pathology, Memorial Sloan-Kettering Cancer Center, Memorial Hospital, 1275 York Avenue, New York, NY 10065, United States (Vollenhoven) Monash Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton, VIC 3168, Australia | Issue Date: | 1-Aug-2013 | Copyright year: | 2013 | Publisher: | BioScientifica Ltd. (Euro House, 22 Apex Court, Woodlands, Bradley Stoke, Bristol BS32 4JT, United Kingdom) | Place of publication: | United Kingdom | Publication information: | Reproduction. 146 (2) (pp 91-102), 2013. Date of Publication: August 2013. | Abstract: | Uterine fibroids are the most common benign tumour afflicting women of reproductive age. Despite the large healthcare burden caused by fibroids, there is only limited understanding of the molecular mechanisms that drive fibroid pathophysiology. Although a large number of genes are differentially expressed in fibroids compared with myometrium, it is likely that most of these differences are a consequence of the fibroid presence and are not causal. The aim of this study was to investigate the expression and regulation of NR2F2 and CTNNB1 based on their potential causal role in uterine fibroid pathophysiology. We used real-time quantitative RT-PCR, western blotting and immunohistochemistry to describe the expression of NR2F2 and CTNNB1 in matched human uterine fibroid and myometrial tissues. Primary myometrial and fibroid smooth muscle cell cultures were treated with progesterone and/or retinoic acid (RA) and sonic hedgehog (SHH) conditioned media to investigate regulatory pathways for these proteins. We showed that NR2F2 and CTNNB1 are aberrantly expressed in fibroid tissue compared with matched myometrium, with strong blood vessel-specific localisation. Although the SHH pathway was shown to be active in myometrial and fibroid primary cultures, it did not regulate NR2F2 or CTNNB1 mRNA expression. However, progesterone and RA combined regulated NR2F2 mRNA, but not CTNNB1, in myometrial but not fibroid primary cultures. In conclusion, we demonstrate aberrant expression and regulation of NR2F2 and CTNNB1 in uterine fibroids compared with normal myometrium, consistent with the hypothesis that these factors may play a causal role uterine fibroid development. © 2013 Society for Reproduction and Fertility. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1530/REP-13-0087 | PubMed URL: | 23704310 [http://www.ncbi.nlm.nih.gov/pubmed/?term=23704310] | ISSN: | 1470-1626 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/27484 | Type: | Article | Subjects: | *protein Nr2f2/ec [Endogenous Compound] *protein ctnnb1/ec [Endogenous Compound] unclassified drug sonic hedgehog protein retinoic acid *protein/ec [Endogenous Compound] progesterone CD31 antigen/ec [Endogenous Compound] alpha smooth muscle actin/ec [Endogenous Compound] Western blotting *uterus myoma smooth muscle fiber adult article cell culture comparative study connective tissue controlled study densitometry endothelium cell female human human tissue immunohistochemistry menstrual cycle molecular weight myometrium pathophysiology priority journal real time polymerase chain reaction protein expression article cell culture protein expression real time polymerase chain reaction *uterus myoma Western blotting human tissue human female endothelium cell densitometry smooth muscle fiber immunohistochemistry menstrual cycle molecular weight myometrium pathophysiology priority journal adult comparative study controlled study connective tissue |
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