PMID- 26435001
OWN - NLM
STAT- MEDLINE
DCOM- 20160307
LR  - 20210816
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 338
DP  - 2015 Dec 2
TI  - Bisphenol AF stimulates transcription and secretion of C-X-C chemokine ligand 12 
      to promote proliferation of cultured T47D breast cancer cells.
PG  - 30-6
LID - S0300-483X(15)30039-1 [pii]
LID - 10.1016/j.tox.2015.09.007 [doi]
AB  - Bisphenol AF (4,4'-hexafluoroisopropylidene-2-diphenol, BPAF), an endocrine 
      disruptor, has been shown to stimulate the proliferation of human breast cancer 
      cells. However, the underlying mechanism has not been fully elucidated. We found 
      that BPAF promoted the in vitro proliferation of estrogen receptor alpha 
      (ERalpha)-positive breast cancer cells (T47D and MCF7), but not ERalpha-negative cells 
      (MDA-MB-231 and MDA-MB-435s). BPAF significantly stimulated the proliferation of 
      cultured T47D cell in a dose-dependent manner, and the half-maximal effective 
      concentration (EC50) was approximately 123 nM. We employed lentivirus-mediated 
      short hairpin RNA (shRNA) to knockdown ERalpha and ER antagonist ICI 182780 to 
      inhibit ER activation, which resulted in the repression of BPAF-induced 
      proliferation of T47D and MCF7 cells. We observed that C-X-C chemokine ligand 12 
      (CXCL12) was up-regulated in T47D cells under treatment with BPAF. Quantitative 
      real-time PCR results showed that BPAF caused a time and dose dependent increase 
      in mRNA level of CXCL12. Furthermore, treatment of T47D cells with BPAF increased 
      CXCL12 secretion according to ELISA assay. BPAF-induced CXCL12 transcription and 
      secretion was significantly attenuated by small interfering RNA (siRNA) targeting 
      ERalpha and ICI 182780, indicating BPAF-induced CXCL12 expression is mediated through 
      ERalpha. Notably, knockdown CXCL12 in T47D cells significantly attenuated 
      BPAF-induced cell proliferation. We also observed that inhibition of CXCL12 
      binding to its receptors CXCR4 and CXCR7 by chalcone 4 blocked BPAF-induced cell 
      growth. Our results indicated that CXCL12 facilitated BPAF-induced proliferation 
      of T47D cells. Taken together, our data provided support that BPAF stimulated 
      transcription and secretion of CXCL12 depending on ERalpha, and ERalpha/CXCL12 signaling 
      positively regulated BPAF-induced proliferation of cultured T47D breast cancer 
      cells.
CI  - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved.
FAU - Li, Ming
AU  - Li M
AD  - Department of Central Laboratory, Beijing Center for Disease Control and 
      Prevention, Beijing 100013, China; Beijing Key Laboratory of Diagnostic and 
      Traceability Technologies for Food Poisoning, Beijing Center for Disease Control 
      and Prevention, Beijing 100013, China.
FAU - Han, Xiaoyu
AU  - Han X
AD  - Department of Central Laboratory, Beijing Center for Disease Control and 
      Prevention, Beijing 100013, China; Beijing Key Laboratory of Diagnostic and 
      Traceability Technologies for Food Poisoning, Beijing Center for Disease Control 
      and Prevention, Beijing 100013, China; School of Public Health and Family 
      Medicine, Capital Medical University, Beijing 100013, China.
FAU - Gao, Wenhui
AU  - Gao W
AD  - Department of Central Laboratory, Beijing Center for Disease Control and 
      Prevention, Beijing 100013, China; Beijing Key Laboratory of Diagnostic and 
      Traceability Technologies for Food Poisoning, Beijing Center for Disease Control 
      and Prevention, Beijing 100013, China.
FAU - Chen, Feng
AU  - Chen F
AD  - Capital Medical University Cancer Center, Beijing Shijitan Hospital, Beijing Key 
      Laboratory for Therapeutic Cancer Vaccines, Beijing 100038, China.
FAU - Shao, Bing
AU  - Shao B
AD  - Department of Central Laboratory, Beijing Center for Disease Control and 
      Prevention, Beijing 100013, China; Beijing Key Laboratory of Diagnostic and 
      Traceability Technologies for Food Poisoning, Beijing Center for Disease Control 
      and Prevention, Beijing 100013, China; School of Public Health and Family 
      Medicine, Capital Medical University, Beijing 100013, China. Electronic address: 
      shaobingch@sina.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151003
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (ACKR3 protein, human)
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (CXCL12 protein, human)
RN  - 0 (CXCR4 protein, human)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (ESR1 protein, human)
RN  - 0 (Endocrine Disruptors)
RN  - 0 (Estrogen Antagonists)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Phenols)
RN  - 0 (Receptors, CXCR)
RN  - 0 (Receptors, CXCR4)
RN  - OH7IX8A37J (4,4'-hexafluorisopropylidene diphenol)
SB  - IM
MH  - Benzhydryl Compounds/*toxicity
MH  - Breast Neoplasms/genetics/*metabolism/pathology
MH  - Cell Proliferation/*drug effects
MH  - Chemokine CXCL12/genetics/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Endocrine Disruptors/*toxicity
MH  - Estrogen Antagonists/pharmacology
MH  - Estrogen Receptor alpha/agonists/genetics/metabolism
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - MCF-7 Cells
MH  - Phenols/*toxicity
MH  - RNA Interference
MH  - Receptors, CXCR/metabolism
MH  - Receptors, CXCR4/metabolism
MH  - Signal Transduction/drug effects
MH  - Time Factors
MH  - Transcription, Genetic
MH  - Transfection
MH  - Up-Regulation
OTO - NOTNLM
OT  - BPAF
OT  - Breast cancer cell
OT  - CXCL12
OT  - Cell proliferation
OT  - ERalpha
EDAT- 2015/10/06 06:00
MHDA- 2016/03/08 06:00
CRDT- 2015/10/06 06:00
PHST- 2015/08/20 00:00 [received]
PHST- 2015/09/28 00:00 [revised]
PHST- 2015/09/28 00:00 [accepted]
PHST- 2015/10/06 06:00 [entrez]
PHST- 2015/10/06 06:00 [pubmed]
PHST- 2016/03/08 06:00 [medline]
AID - S0300-483X(15)30039-1 [pii]
AID - 10.1016/j.tox.2015.09.007 [doi]
PST - ppublish
SO  - Toxicology. 2015 Dec 2;338:30-6. doi: 10.1016/j.tox.2015.09.007. Epub 2015 Oct 3.