PMID- 32432040
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 10
DP  - 2020
TI  - FGFR2/STAT3 Signaling Pathway Involves in the Development of MMTV-Related 
      Spontaneous Breast Cancer in TA2 Mice.
PG  - 652
LID - 10.3389/fonc.2020.00652 [doi]
LID - 652
AB  - The Tientsin Albino 2 (TA2) mouse has a high incidence of spontaneous breast 
      cancer (SBC) in the absence of external inducers or carcinogens. The initiation 
      of SBC is related to mouse mammary tumor virus (MMTV) infection and pregnancy. 
      Pathologic analysis showed that breast cancer cells in TA2 mice are triple 
      negative. Our previous study confirmed that fibroblast growth factor receptor 2 
      (FGFR2) expression increased in SBC tissue compared to that in their 
      corresponding normal breast tissues of TA2 mice. The present study focused on the 
      function of the FGFR2/STAT3 signaling pathway in the initiation of SBC. In this 
      study, the expression of FGF3, FGFR2, STAT3, p-STAT3(Tyr705), and p-STAT3(Ser727) 
      was detected in serum and normal mammary gland tissues of TA2 mice with different 
      number of pregnancies and SBC. The proliferation, invasiveness, and migration 
      abilities of MA-891 cells from TA2 SBC were compared before and after 
      cryptotanshinone and Stattic treatment. Transient siRNA transfection was used to 
      detect the invasiveness, and migration abilities to avoid the off-targets 
      effects. Downstream protein expression of STAT3 was also detected in MA-891 cells 
      and TA2 xenografts from MA-891 inoculation. In addition, STAT3 expression was 
      analyzed in 139 cases of human breast cancer including 117 cases of non-triple 
      negative breast cancer (non-TNBC) (group I) and 22 cases of triple-negative 
      breast cancer (TNBC) (group II). Results of our study confirmed that MMTV-LTR 
      amplification, and FGFR2, p-STAT3(Tyr705), p-STAT3(Ser727) expression increased 
      with the number of pregnancies in the breast tissue of TA2 mice and were the 
      highest in SBC. Serum FGF3 expression of SBC was higher than it of TA2 mice with 
      different number of pregnancies. After STAT3 was inhibited, the abilities of 
      proliferation, invasiveness, and migration in MA-891 decreased and the expression 
      levels of STAT3, p-STAT3(Ser727), p-STAT3(Tyr705), Bcl2, cyclin D1, and c-myc in 
      MA-891 and animal xenografts were also down-regulated. In human breast cancer, 
      STAT3 expression was significantly higher in TNBC than that in non-TNBC. Our 
      results showed that the FGFR2/STAT3 signaling pathway may be related to SBC 
      initiation in TA2 mice. Inhibition of STAT3 can decrease proliferation, 
      invasiveness, and migration in MA-891 cells and the growth of TA2 xenografts.
CI  - Copyright (c) 2020 Du, Zhao, Liu, Li, Fu, Zhang, Zhang, Zheng, Zhao and Zhang.
FAU - Du, Jiaxing
AU  - Du J
AD  - Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, 
      China.
AD  - Department of Pathology, Tianjin Union Medical Center, Tianjin, China.
FAU - Zhao, Qi
AU  - Zhao Q
AD  - Department of Pathology, Tianjin Union Medical Center, Tianjin, China.
AD  - Graduate School, Tianjin Medical University, Tianjin, China.
FAU - Liu, Kai
AU  - Liu K
AD  - Department of Pathology, Tianjin Union Medical Center, Tianjin, China.
AD  - Graduate School, Tianjin Medical University, Tianjin, China.
FAU - Li, Zugui
AU  - Li Z
AD  - Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, 
      China.
AD  - Department of Pathology, Tianjin Union Medical Center, Tianjin, China.
FAU - Fu, Fangmei
AU  - Fu F
AD  - Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, 
      China.
AD  - Department of Pathology, Tianjin Union Medical Center, Tianjin, China.
FAU - Zhang, Kexin
AU  - Zhang K
AD  - Department of Pathology, Tianjin Union Medical Center, Tianjin, China.
AD  - Nankai University School of Medicine, Nankai University, Tianjin, China.
FAU - Zhang, Hao
AU  - Zhang H
AD  - Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, 
      China.
AD  - Department of Pathology, Tianjin Union Medical Center, Tianjin, China.
FAU - Zheng, Minying
AU  - Zheng M
AD  - Department of Pathology, Tianjin Union Medical Center, Tianjin, China.
FAU - Zhao, Yongjie
AU  - Zhao Y
AD  - Departments of General Surgery, Tianjin Union Medical Center, Tianjin, China.
FAU - Zhang, Shiwu
AU  - Zhang S
AD  - Department of Pathology, Tianjin Union Medical Center, Tianjin, China.
LA  - eng
PT  - Journal Article
DEP - 20200505
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC7214838
OTO - NOTNLM
OT  - FGFR2/STAT3
OT  - MMTV
OT  - spontaneous breast cancer
OT  - tientsin albino 2
OT  - triple-negative breast cancer
EDAT- 2020/05/21 06:00
MHDA- 2020/05/21 06:01
PMCR- 2020/01/01
CRDT- 2020/05/21 06:00
PHST- 2020/01/31 00:00 [received]
PHST- 2020/04/07 00:00 [accepted]
PHST- 2020/05/21 06:00 [entrez]
PHST- 2020/05/21 06:00 [pubmed]
PHST- 2020/05/21 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2020.00652 [doi]
PST - epublish
SO  - Front Oncol. 2020 May 5;10:652. doi: 10.3389/fonc.2020.00652. eCollection 2020.