PMID- 37496658
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230728
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 13
DP  - 2023
TI  - Fibroblast growth factor 3 promotes spontaneous mammary tumorigenesis in Tientsin 
      albino 2 mice via the FGF3/FGFR1/STAT3 pathway.
PG  - 1161410
LID - 10.3389/fonc.2023.1161410 [doi]
LID - 1161410
AB  - INTRODUCTION: Tientsin albino 2 (TA2) mice can develop spontaneous breast cancer 
      (SBC), which is associated with multiple pregnancies and infection with the mouse 
      mammary tumor virus (MMTV). In this study, we sought to elucidate the molecular 
      mechanisms underlying the development of SBC in TA2 mice induced by MMTV. 
      METHODS: The integration site of MMTV in TA2 SBC was identified using 
      whole-genome sequencing. The expression of fibroblast growth factor 3 (FGF3) in 
      SBCs and normal breast tissues was compared. The primary cell line, TA-1106, 
      derived from SBC, was cultured. The proliferation, cell cycle, migration, 
      invasion, and tumorigenicity abilities, as well as the expression of 
      epithelial-mesenchymal transition-related proteins, phosphorylated STAT3, and 
      phosphorylated Akt, were assessed in MA-891cell line from TA2 and TA-1106 cells 
      after FGF3 knockdown. The binding of FGF3 to FGF receptor 1 (FGFR1) was 
      determined by co-immunoprecipitation. Additionally, the relationship between 
      STAT3 and Akt phosphorylation was investigated using a small molecule inhibitor 
      and STAT3 knockdown. RESULTS: MMTV integrated upstream of the FGF3 gene, and the 
      FGF3 protein was highly expressed in TA2 SBCs. FGF3 knockdown in MA-891 and 
      TA-1106 decreased their proliferation, migration, and invasion abilities, 
      affected the cell cycle and expression of epithelial-mesenchymal 
      transition-related proteins, and inhibited the growth of animal xenografts. FGF3 
      binds to FGFR1, and either FGF3 or FGFR1 knockdown decreases STAT3 and Akt 
      phosphorylation levels. Inhibition of phosphorylation or expression of STAT3 
      resulted in decreased Akt phosphorylation levels. Inhibition of Akt 
      phosphorylation also resulted in decreased STAT3 phosphorylation levels. 
      Furthermore, treatment of MA-891 and TA-1106 cells with Wortmannin or Stattic 
      caused FGFR1 upregulation in addition to inhibiting Akt or STAT3 phosphorylation. 
      CONCLUSION: The results of this study demonstrate that FGF3 plays a significant 
      role in the development of SBC through the FGF3/FGFR1/STAT3 signaling pathway. 
      There is a reciprocal activation between STAT3 and Akt. Inhibition of STAT3 or 
      Akt phosphorylation promoted the expression of FGFR1. Validating the conclusions 
      obtained in this study in human breast cancer (HBC) may contribute to targeted 
      therapy and it is worth exploring whether the homologous sequences of MMTV in HBC 
      have a similar oncogenic effect.
CI  - Copyright (c) 2023 Chen, Zhang, Liu, Chen, Zheng, Zhu and Zhang.
FAU - Chen, Lankai
AU  - Chen L
AD  - Nankai University School of Medicine, Nankai University, Tianjin, China.
FAU - Zhang, Xipeng
AU  - Zhang X
AD  - Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China.
FAU - Liu, Guisheng
AU  - Liu G
AD  - Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China.
FAU - Chen, Shuo
AU  - Chen S
AD  - Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China.
FAU - Zheng, Minying
AU  - Zheng M
AD  - Department of Pathology, Tianjin Union Medical Center, Tianjin, China.
FAU - Zhu, Siwei
AU  - Zhu S
AD  - Nankai University School of Medicine, Nankai University, Tianjin, China.
AD  - Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China.
FAU - Zhang, Shiwu
AU  - Zhang S
AD  - Nankai University School of Medicine, Nankai University, Tianjin, China.
AD  - Department of Pathology, Tianjin Union Medical Center, Tianjin, China.
LA  - eng
PT  - Journal Article
DEP - 20230711
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC10367089
OTO - NOTNLM
OT  - MA-891
OT  - Tientsin albino 2
OT  - fibroblast growth factor 3
OT  - mouse mammary tumor virus
OT  - spontaneous breast cancer
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/07/27 06:42
MHDA- 2023/07/27 06:43
PMCR- 2023/01/01
CRDT- 2023/07/27 03:59
PHST- 2023/02/08 00:00 [received]
PHST- 2023/06/13 00:00 [accepted]
PHST- 2023/07/27 06:43 [medline]
PHST- 2023/07/27 06:42 [pubmed]
PHST- 2023/07/27 03:59 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2023.1161410 [doi]
PST - epublish
SO  - Front Oncol. 2023 Jul 11;13:1161410. doi: 10.3389/fonc.2023.1161410. eCollection 
      2023.