PMID- 28404976
OWN - NLM
STAT- MEDLINE
DCOM- 20180607
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 24
DP  - 2017 Jun 13
TI  - Estrogen enhances mismatch repair by induction of MLH1 expression via estrogen 
      receptor-beta.
PG  - 38767-38779
LID - 10.18632/oncotarget.16351 [doi]
AB  - Epidemiological data demonstrated that hormone replace treatment has protective 
      effect against colorectal cancer (CRC). Our previous studies showed that this 
      effect may be associated with DNA mismatch repair. This study aims to investigate 
      the mechanism of estrogen induction of MLH1, and whether colorectal tumor 
      proliferation can be inhibited through induction of MLH1 by estrogen signal 
      pathway. Human CRC cell lines were used to examine the regulation of MLH1 
      expression by over-expression and depletion of estrogen receptor-alpha (ERalpha) and 
      estrogen receptor-beta (ERbeta), under the treatment with 17beta-estradiol or beta-Estradiol 
      6-(O-carboxy-methyl)oxime:BSA, followed by a real-time Q-PCR and Western blotting 
      analysis. Luciferase reporter and chromatin immunoprecipitation assays were used 
      to identify the estrogen response elements in the proximal promoter of MLH1 gene. 
      Then, the influence of estrogen-induced MLH1 on CRC tumor growth were determined 
      in vitro and in vivo. We found that mismatch repair ability and microsatellite 
      stability of cells were enhanced by estrogen via induction of MLH1 expression, 
      which was mediated by ERbeta, through a transcriptional activation process. 
      Furthermore, we identified that ERbeta exerted an inhibitory effect on CRC tumor 
      proliferation in vitro and in vivo, combined with 5-FU, through up-regulation of 
      MLH1 expression. Finally, we concluded that estrogen enhances mismatch repair 
      ability and tumor inhibition effect in vitro and in vivo, via induction of MLH1 
      expression mediated by ERbeta.
FAU - Lu, Jun-Yu
AU  - Lu JY
AD  - Third Military Medical University, Chongqing, China, 400038.
AD  - Department of Gastroenterology, PLA Army General Hospital, Beijing, China, 
      100700.
FAU - Jin, Peng
AU  - Jin P
AD  - Department of Gastroenterology, PLA Army General Hospital, Beijing, China, 
      100700.
FAU - Gao, Wei
AU  - Gao W
AD  - Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical 
      University, Dalian, China, 116044.
FAU - Wang, De-Zhi
AU  - Wang DZ
AD  - Department of Gastroenterology, PLA Army General Hospital, Beijing, China, 
      100700.
FAU - Sheng, Jian-Qiu
AU  - Sheng JQ
AD  - Department of Gastroenterology, PLA Army General Hospital, Beijing, China, 
      100700.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Estrogens)
RN  - 0 (MLH1 protein, human)
RN  - EC 3.6.1.3 (MutL Protein Homolog 1)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Biomarkers, Tumor/genetics/*metabolism
MH  - Cell Proliferation
MH  - Colorectal Neoplasms/*genetics/metabolism/pathology
MH  - DNA Mismatch Repair/*genetics
MH  - Estrogen Receptor beta/genetics/*metabolism
MH  - Estrogens/*pharmacology
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Humans
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - MutL Protein Homolog 1/genetics/*metabolism
MH  - Promoter Regions, Genetic
MH  - Response Elements
MH  - Transcription, Genetic
MH  - Tumor Cells, Cultured
MH  - Xenograft Model Antitumor Assays
PMC - PMC5503570
OTO - NOTNLM
OT  - MLH1
OT  - colorectal cancer
OT  - estrogen
OT  - estrogen receptor beta
OT  - mismatch repair
COIS- CONFLICTS OF INTEREST The authors have no conflict of interest.
EDAT- 2017/04/14 06:00
MHDA- 2018/06/08 06:00
PMCR- 2017/06/13
CRDT- 2017/04/14 06:00
PHST- 2016/07/22 00:00 [received]
PHST- 2017/01/03 00:00 [accepted]
PHST- 2017/04/14 06:00 [pubmed]
PHST- 2018/06/08 06:00 [medline]
PHST- 2017/04/14 06:00 [entrez]
PHST- 2017/06/13 00:00 [pmc-release]
AID - 16351 [pii]
AID - 10.18632/oncotarget.16351 [doi]
PST - ppublish
SO  - Oncotarget. 2017 Jun 13;8(24):38767-38779. doi: 10.18632/oncotarget.16351.