Table 1 Breast cancer findings for environmental chemical disruptors in experimental studies that investigated cancer progression and targeted signal pathways
From: Environmental chemicals, breast cancer progression and drug resistance
Potential environmental chemical disruptors | Studies (ref) | Type of study (in vitro/in vivo) | Effects that chemicals may have | Targeted signal pathways |
|---|---|---|---|---|
Persistent EDCs | ||||
 Dioxin | [9] | In vivo | ↓ tumor growth in immature 120-150 g female Sprague-Dawley rat (no more precision) | Unestablished |
[10] | In vitro | ↓ invasion, motility and colony formation (MDA-MB-231, MCF7, ZR75, SKBR3) ↑ differenciation in a putative mammary cancer stem cell line | AhR dependant pathway regardless to ER status | |
[11] | In vivo/ In vitro | ↓ proliferation (MCF7) ↓ tumor growth in male B6D2F mice ( | Antagonistic effect on ER signaling | |
[12] | In vitro | ↓ proliferation (MCF7, TD47, ZR75) | Antagonistic effect on ER signaling | |
[13] | In vitro | ↓ migration (MCF7) | Downregulation of CXCR4 and CXCL12 | |
[14] | In vivo/ In vitro | ↓ metastasis formation in BALB/C mice (from NCI Charles Rivers, Frederick, MD, USA) No effect on tumor growth nor cell proliferation | Unestablished | |
[15] | In vitro | ↑ cell migration | NFATc1/ATX-signaling pathway | |
[16] | In vitro | EMT, ↑ migration | AhR pathway | |
[17] | In vitro | ↑ invasion Resistance to apoptosis Mitochondrial dysfonction (↑ cytosolic [Ca(2+)](c) and RyR1-specific Ca(2+) release, ↑ calcineurin (CnA) levels and activation of its factors. | Mitochondrial transmembrane potential disruption in a time-dependent way Mitochondrial transcription and translation inhibition Activation of CnA-sensitive NF-kappaB/Rel (IkappaBbeta-dependent) factors. | |
[18] | In vivo/ In vitro | ↓ colony formation (BP1, Hs578T, SUM149) ↑ migration ↓ metastasis (2-days zebrafish larvae AB x Fli-GFP) | AhR signaling pathway | |
 Polychlorinated biphenyls | [19] | In vivo/ In vitro | ↑ migration (MCF7, MDA-MB-231 ↑ growth tumor and metastasis in NOD SCID immune- deficient mice (no more precision) | ROCK signaling pathway |
[20] | In vitro | ↑ transendothelial migration (MDA-MB-231) | Overexpression of VEGF through PI3K pathway signaling | |
[21] |  | ↑ transendothelial migration, ↑MMP3 (human endothelial cells) | Activation EGFR and JAK3 in a coordinated and cross-regulated way AK3 and EGFR stimulate in concert PCB-induced activation of JNK and ERK1/2 followed by increased DNA binding of AP-1 and PEA3 and transcriptional up-regulation of MMP-3 expression. | |
DDT/DDE and organochlorine pesticides | ||||
 DDT/DDE | [22] | In vivo | ↑ ER + tumor growth in 150 g Wistar Furth ovariectomized rat (from Harlan Sprague Dawley, Madison, WI) ↑ proliferation MT2 and MTW9/PL estrogen responsive mammary adenocarcinoma | ER signaling pathway Estrogen-androgen balance disruption |
[23] | In vitro | ↑ proliferation in CAMA-1 human ER+ breast cancer cells | Opposing androgen signalling pathway that inhibits growth in hormone-responsive | |
 Hexachlorobenzene | [24] | In vitro | ↑ proliferation (MCF7) | IGF-I) signaling pathway |
[25] | In vitro | ↑ migration (MDA-MB-231) | c-Src/HER1/STAT5b and HER1/ERK1/2 signaling pathways | |
[26] | In vivo/ In vitro | ↑ invasion and MMP2/9 (MDA-MB-231) ↑ metastasis in mice (regardless ER status) in nude female Swiss BALB/C mice (La Plata Laboratory Animal Facility, Buenos Aires, Argentina) | AhR, c-Src, HER1, STAT5b, and ERK1/2 signaling pathways | |
[27] | In vitro | ↑ migration and invasion | Modulation of the crosstalk between AhR and TGFβ signaling | |
Consumer product chemicals | ||||
 Bisphenol A | [28] | In vitro | ↑ expression MMP2/ MMP9 in TNBC –triple negative breast cancer (MDA-MB-231 and BT-549) | Activation ERRγ through ERK1/2 and Akt pathway |
[29] | In vitro | ↑ proliferation and invasion in TNBC –triple negative breast cancer (MDA-MB-231 and BT-549) | Unestablished | |
In vitro | ↑ proliferation (MCF7) | Upregulation of cell cycle genes Downregulation of antiproliferative genes | ||
[32] | In vitro | Alteration of the expression of cell cycle related genes | Activation of Estrogen Receptor dependent signaling pathway | |
[33] | In vitro | ↑ proliferation Induction of a profile of tumor aggressiveness in high-risk cells from breast cancer patients | Unestablished | |
In vitro | ↑ migration and invasion (MDA-MB-231) | Activation GPER dependant pathway Activation of FAK, Src, ERK2-dependant pathway | ||
 Phtalates | [36] | In vitro | Phenotypical and gene expression changes associated with EMT (R2d cells, stem cell derived human breast epithelial cell line) | Activation of EGFR-PKA signaling cascade that increase AP2a transcriptor factor which upregulate histone deacetylase 3 |
[37] | In vitro/In vivo | ↑ proliferation, migration and colony formation (MDA-MB-231) ↑ tumor formation in Female nude mice BALB/cAnN.Cg-Foxn1nu/CrlNarl, 4–6 wk. old (from the National Laboratory Animal Center Taipei, Taiwan) | AhR/HDAC6/c-Myc signaling pathway | |
[38] | In vitro | ↑ proliferation (MCF7) | Activation of PPARα and γ | |
[39] | In vitro | ↑ proliferation (MCF7) | P13K/AKT signaling pathway | |
[40] | In vitro | ↓ tamoxifen-induced apoptosis in ER+ cells (MCF7) but not ER- cells (MDA-MB-231 | Increased Bcl-2 to Bax ratio through an Estrogen Receptor dependent signaling pathway | |
 Benzophénone-1/Nonylphenol | [41] | In vitro | ↑ proliferation and migration (MCF7) | Upregulation of cyclin D1 and cathepsin D and downregulation in p21 regulated by an ERα-dependent pathway |
 Per and polyfluoroalkyl acids | ||||
  PFOA | [42] | In vitro | ↑ proliferation, migration and invasion (MCF10) | Upregulation of cyclin D1 and CDK4/6 and downregulation and in p27 through PPARα-dependant pathway |
  PFOS | [43] | In vitro | ↑ proliferation, migration and invasion (MCF10) | Upregulation of CDK4 and down regulation and downregulation in p27, p21 and p53 |
Food preparation | ||||
 Benzo(A)pyrene | [35] | In vitro | ↑ migration (MDA-MB-231, MCF7) ↑ αvβ3 integrin-cell surface levels and an increase of metalloproteinase (MMP)-2 and MMP-9 | Lipoxygenase- and Src-dependent pathway Activation of FAK, Src and extracellular signal-regulated kinase 2 |
[44] | In vitro | ↑ invasion (MDA-MB-231) | Upregulation of COX II and PGE2 through an AhR signaling pathway | |
[45] | In vivo/In vitro | ↑ migration and invasion, ↑MMP9 (MCF7) ↑ growth tumor and liver and lung metastasis in an accumulative mouse model mimicking the cumulative effects of chronic BaP exposure in female BALB/C mice (from the Shanghai Laboratory Animal, China) | Upregulation of ROS-induced ERK signaling pathway | |
 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine | [46] | In vitro | ↑ migration and invasion, ↑ MMP9 (MCF7, TD47) | Upregulation of Cathepsin D and cyclooxygenase 2 through ER signaling |
[47] | In vivo/In vitro | Carcinogenesis effects, ↑ proliferation, migration, invasion, ↑ colony formation and stem-like cell populations (MCF10) ↑tumorigenicity, ↑ lung metastasis in athymic NCS-nu/nu mice ((no more precision) | Ras-ERK-Nox-ROS signaling pathway | |
Other polycyclic aromatic carbons | ||||
 Cigarette smoke | [48] | In vivo | ↑ total pulmonary metastatic burden in smoke-exposed animals (female sexually mature BALB/cAnN mice) (from Charles River Laboratories, Wilmington, MA, USA) | Unestablished |
[49] | In vitro/ In vivo | Phenotypical and gene expression changes associated with EMT (MCF7) Emergence of stem-like cells population, colony formation ↓ tumor size ↑ lung metastasis and liver cancer cells in female immuno deficient NSG mice (from The Jackson Laboratory, Bar Harbor, ME, USA) | Unestablished Activation of nAChRs, Src and calcium-dependent signaling pathway | |
[50] | In vitro | ↑ proliferation and invasion ↑ migration in a dose-dependent manner Phenotypical and gene expression changes associated with EMT (MCF7 and MDA-MB-468) | Unestablished | |
[51] | In vitro | ↑ proliferation ↑ of stem-like cells population Resistance to Doxorubicin |  | |
 7,12-dimethylbenz(a)anthracene | [52] | In vitro | ↑ proliferation and invasion (mice) ↑ colony formation EMT (↓ E cadherin) | NFκB pathway |
Alcohol | [53] (review) | In vitro/ in vivo | ↑Angiogenesis, migration, invasion, EMT, MMP ↑ Cancer stem cells ↑ Metastasis formation in MMTV neu transgenic mice (no more precision) | Cross-talk between oxidative stress and EGFR/ErbB2 signaling |
Toxic metals | [54] | In vitro | Cadmium ↑ migration and invasion (MCF7, MDA-MB-231) | TGIF/MMP2 signaling axis |
[55] | In vivo/ In vitro | Tungsten ↓ primary tumor growth but ↑metastasis in female BALB/C mice No change observed in invasiveness of cells in vitro (66Cl4 model of breast cancer metastasis to bone) (from Charles Rivers Laboratories, Montréal, Canada) | Targeting microenvironment: activation CAFs at the metastatic site (↑ MMP9) and ↑ of myeloid-derived suppressor cells | |