title: Bisphenol AF stimulates transcription and secretion of C-X-C chemokine ligand 12 to promote proliferation of cultured T47D breast cancer cells.
abstract: 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 α (ERα)-positive breast cancer cells (T47D and MCF7), but not ERα-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 ERα 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 ERα and ICI 182780, indicating BPAF-induced CXCL12 expression is mediated through ERα. 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 ERα, and ERα/CXCL12 signaling positively regulated BPAF-induced proliferation of cultured T47D breast cancer cells.
authors.affiliation: 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.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Han
authors.affiliation: 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.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Gao
authors.affiliation: Capital Medical University Cancer Center, Beijing Shijitan Hospital, Beijing Key Laboratory for Therapeutic Cancer Vaccines, Beijing 100038, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Bing
authors.initials: B
authors.lastname: Shao
mesh_terms: D001559:Benzhydryl Compounds / Q000633:toxicity*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells; D010636:Phenols / Q000633:toxicity*; D034622:RNA Interference; D054387:Receptors, CXCR / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation; D005466:Fluorocarbons; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D054377:Chemokine CXCL12; D052244:Endocrine Disruptors; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D010636:Phenols; D054387:Receptors, CXCR; D019718:Receptors, CXCR4; C501896:ACKR3 protein, human; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; C506487:ESR1 protein, human; C583074:bisphenol AF; D005466:Fluorocarbons; D000098826:Bisphenol A Compounds
keywords: BPAF; Breast cancer cell; CXCL12; Cell proliferation; ERα