PMID- 28637297
OWN - NLM
STAT- MEDLINE
DCOM- 20171012
LR  - 20181113
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 102
IP  - 9
DP  - 2017 Sep 1
TI  - A Role for Progesterone-Regulated sFRP4 Expression in Uterine Leiomyomas.
PG  - 3316-3326
LID - 10.1210/jc.2016-4014 [doi]
AB  - CONTEXT: Despite progesterone's key role in uterine smooth muscle tumorigenesis, 
      the mechanisms by which it promotes the growth of uterine leiomyomas remain 
      poorly understood. OBJECTIVE: The aim of this study was to identify gene products 
      mediating the effects of progesterone in uterine leiomyomas. DESIGN: Gene 
      expression profiling was used to identify putative progesterone-regulated genes 
      differentially expressed in uterine leiomyomas, which were then studied in vitro. 
      METHODS: Gene expression was comprehensively profiled with the Illumina WG 
      BeadChip (version 2.6) and analyzed with a bioinformatic algorithm that 
      integrates known protein-protein interactions. Genomic binding sites for 
      progesterone receptor (PR) were interrogated by chromatin 
      immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR). Small 
      interfering RNA was used to study gene function in primary cell lines. RESULTS: 
      Our analyses identified secreted Frizzled-related protein 4 (sFRP4) as a key gene 
      product functionally linked to PR activation whose expression was 2.6 times 
      higher in leiomyomas than myometrium (n = 26, P < 0.01) and 2.5 times higher 
      during the proliferative phase of the menstrual cycle (n = 26, P < 0.01). Direct 
      binding between PR and sFRP4 promoter was observed by ChIP-qPCR. Robust 
      overexpression of sFRP4 was also observed in primary cultures derived from 
      leiomyoma. Progesterone preferentially inhibited sFRP4 expression and secretion 
      in leiomyoma cultures in a dose-dependent manner sensitized by estradiol. 
      Knockdown of sFRP4 inhibited proliferation and apoptosis in primary cultures of 
      both myometrium and leiomyoma. CONCLUSIONS: Overexpression of sFRP4 is a robust, 
      progesterone-regulated feature of leiomyomas that increases smooth muscle 
      proliferation. More work is needed to elucidate how progesterone's ability to 
      modulate sFRP4 expression contributes to uterine smooth muscle tumorigenesis.
CI  - Copyright (c) 2017 Endocrine Society
FAU - Delaney, Meaghan A
AU  - Delaney MA
AD  - Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, Texas 
      77030.
FAU - Wan, Ying-Wooi
AU  - Wan YW
AD  - Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, Texas 
      77030.
AD  - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, 
      Texas 77030.
FAU - Kim, Gyoung-Eun
AU  - Kim GE
AD  - Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, Texas 
      77030.
FAU - Creighton, Chad J
AU  - Creighton CJ
AD  - Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, 
      Texas 77030.
FAU - Taylor, Margaret G
AU  - Taylor MG
AD  - Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, Texas 
      77030.
FAU - Masand, Ramya
AU  - Masand R
AD  - Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas 
      77030.
FAU - Park, Andrew
AU  - Park A
AD  - Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, Texas 
      77030.
FAU - Valdes, Cecilia
AU  - Valdes C
AD  - Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, Texas 
      77030.
FAU - Gibbons, William
AU  - Gibbons W
AD  - Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, Texas 
      77030.
FAU - Liu, Zhandong
AU  - Liu Z
AD  - Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, 
      Texas 77030.
AD  - Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030.
FAU - Anderson, Matthew L
AU  - Anderson ML
AD  - Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, Texas 
      77030.
AD  - Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, 
      Texas 77030.
AD  - Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas 
      77030.
LA  - eng
GR  - R01 GM120033/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (SFRP4 protein, human)
RN  - 4G7DS2Q64Y (Progesterone)
SB  - IM
MH  - Biopsy, Needle
MH  - Blotting, Western
MH  - Cell Proliferation/genetics
MH  - Disease Progression
MH  - Female
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunohistochemistry
MH  - Leiomyoma/*genetics/pathology
MH  - Myocytes, Smooth Muscle/physiology
MH  - Progesterone/*metabolism
MH  - Promoter Regions, Genetic/genetics
MH  - Proto-Oncogene Proteins/*genetics
MH  - RNA, Messenger/metabolism
MH  - Real-Time Polymerase Chain Reaction/methods
MH  - Role
MH  - Uterine Neoplasms/*genetics/pathology
PMC - PMC5587057
EDAT- 2017/06/24 06:00
MHDA- 2017/10/13 06:00
PMCR- 2018/09/01
CRDT- 2017/06/23 06:00
PHST- 2016/12/22 00:00 [received]
PHST- 2017/06/09 00:00 [accepted]
PHST- 2017/06/24 06:00 [pubmed]
PHST- 2017/10/13 06:00 [medline]
PHST- 2017/06/23 06:00 [entrez]
PHST- 2018/09/01 00:00 [pmc-release]
AID - 3868126 [pii]
AID - jcem_20164014 [pii]
AID - 10.1210/jc.2016-4014 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2017 Sep 1;102(9):3316-3326. doi: 10.1210/jc.2016-4014.