Perfluorooctanoic acid (PFOA) exposure promotes proliferation, migration and invasion potential in human breast epithelial cells

Pierozan, Paula; Jernerén, Fredrik; Karlsson, Oskar

doi:10.1007/s00204-018-2181-4

Cited by 97 publications

(36 citation statements)

References 57 publications

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“…The biological plausibility is supported by limited yet consistent cell‐based mechanistic studies. For instance, the exposure of PFOS at 1–10 μM stimulated in a dose‐dependent manner the proliferation, migration and invasiveness of immortalized BC cells MCF‐10A, through the upregulation of CDK4 and downregulation of p27, p21 and p53 . The authors did not find any alteration of ERα and ERβ levels; nonetheless, the cell proliferation was partially blocked when cells were co‐exposed to an ER receptor inhibitor.…”

Section: Discussionmentioning

confidence: 92%

“…For instance, the exposure of PFOS at 1-10 μM stimulated in a dose-dependent manner the proliferation, migration and invasiveness of immortalized BC cells MCF-10A, through the upregulation of CDK4 and downregulation of p27, p21 and p53. 23,24 The authors did not find any alteration of ERα and ERβ levels; nonetheless, the cell proliferation was partially blocked when cells were co-exposed to an ER receptor inhibitor. On this regard, the authors suggested other alternative mechanisms contributed to explain the effects triggered by PFOS such as the pathway involving the growth factor receptor EGFR/HER2.…”

Section: Modelmentioning

confidence: 96%

See 1 more Smart Citation

Perfluorinated alkylated substances serum concentration and breast cancer risk: Evidence from a nested case‐control study in the French E3N cohort

Mancini

Cano-Sancho

Gambaretti

et al. 2019

Intl Journal of Cancer

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Endocrine‐disrupting chemicals are proposed to increase breast cancer (BC) incidence. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), two perfluorinated alkylated substances (PFASs), are suspected to be ubiquitously present in the blood of human population worldwide. We investigated the associations between serum concentrations of these substances and BC risk. Etude Epidémiologique auprès de femmes de l'Education Nationale is a cohort of 98,995 French women born in 1925–1950 and followed up since 1990. We sampled 194 BC cases and 194 controls from women with available blood samples. Serum concentrations of PFASs were measured by liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS). Adjusted conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two sided. While PFASs concentrations were not associated with BC risk overall, we found positively linear associations between PFOS concentrations and the risk of ER+ (3rd quartile: OR = 2.22 [CI = 1.05–4.69]; 4th quartile: OR = 2.33 [CI = 1.11–4.90]); Ptrend = 0.04) and PR+ tumors (3rd quartile: OR = 2.47 [CI = 1.07–5.65]; 4th quartile: OR = 2.76 [CI = 1.21–6.30]; Ptrend = 0.02). When considering receptor‐negative tumors, only the 2nd quartile of PFOS was associated with risk (ER−: OR = 15.40 [CI = 1.84–129.19]; PR−: OR = 3.47 [CI = 1.29–9.15]). While there was no association between PFOA and receptor‐positive BC risk, the 2nd quartile of PFOA was positively associated with the risk of receptor‐negative tumors (ER−: OR = 7.73 [CI = 1.46–41.08]; PR−: OR = 3.44 [CI = 1.30–9.10]). PFAS circulating levels were differentially associated with BC risk. While PFOS concentration was linearly associated with receptor‐positive tumors, only low concentrations of PFOS and PFOA were associated with receptor‐negative tumors. Our findings highlight the importance of considering exposure to PFASs as a potential risk factor for BC.

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Section: Discussionmentioning

confidence: 92%

Section: Modelmentioning

confidence: 96%

Perfluorinated alkylated substances serum concentration and breast cancer risk: Evidence from a nested case‐control study in the French E3N cohort

Mancini

Cano-Sancho

Gambaretti

et al. 2019

Intl Journal of Cancer

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“…In vitro, the ability of PFAS to influence cell proliferation, particularly in assays of breast and other endocrine mediated cells and tissues has been assessed. PFOA and PFOS both increased proliferation, cell migration and invasion of normal human breast epithelial cells and altered the expression of proteins involved in cell cycle regulation, including cyclin dependent kinase 4 [202,203]. Similarly, in a mixture with two other chemicals found in consumer products, environmentally relevant concentrations of PFOA increased cell proliferation in non-malignant breast cancer cells through cell cycle disruption, reduced cell apoptosis and increased estrogen receptor alpha levels [204].…”

Section: Alters Cell Proliferation Cell Death or Nutrient Supplymentioning

confidence: 97%

“…PFOA Association: [61] Association: [202]; [204]; [205]; [207]; [209] Long-chain PFAS a PFOS Association: [203]; [207]; [208]…”

Section: Epidemiological Animal Biosassay In Vitromentioning

confidence: 99%

Application of the Key Characteristics of Carcinogens to Per and Polyfluoroalkyl Substances

Temkin

Hocevar

Andrews

et al. 2020

IJERPH

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Per- and polyfluoroalkyl substances (PFAS) constitute a large class of environmentally persistent chemicals used in industrial and consumer products. Human exposure to PFAS is extensive, and PFAS contamination has been reported in drinking water and food supplies as well as in the serum of nearly all people. The most well-studied member of the PFAS class, perfluorooctanoic acid (PFOA), induces tumors in animal bioassays and has been associated with elevated risk of cancer in human populations. GenX, one of the PFOA replacement chemicals, induces tumors in animal bioassays as well. Using the Key Characteristics of Carcinogens framework for cancer hazard identification, we considered the existing epidemiological, toxicological and mechanistic data for 26 different PFAS. We found strong evidence that multiple PFAS induce oxidative stress, are immunosuppressive, and modulate receptor-mediated effects. We also found suggestive evidence indicating that some PFAS can induce epigenetic alterations and influence cell proliferation. Experimental data indicate that PFAS are not genotoxic and generally do not undergo metabolic activation. Data are currently insufficient to assess whether any PFAS promote chronic inflammation, cellular immortalization or alter DNA repair. While more research is needed to address data gaps, evidence exists that several PFAS exhibit one or more of the key characteristics of carcinogens.

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“…PFOA has also been detected in the blood in several industrialized countries. Exposure to PFOA may be associated with several adverse effects, and recent epidemiological studies have linked its toxicity to tumorigenic processes in the liver, pancreas, breast and testicles (3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Perfluorooctanoic acid induces migration and invasion and inhibits apoptosis through the PI3K/AKT signaling pathway in human rhabdomyosarcoma cells

et al. 2019

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The present study aimed to investigate the effects of perfluorooctanoic acid (PFOA) on tumor cell migration, invasion and apoptosis by activation of the PI3K/AKT signaling pathway in human rhabdomyosarcoma (RMS). PFOA is a persistent, synthetic organic environment pollutant, which has been previously associated with multiple diseases, including cancer. The present study aimed to confirm whether PFOA can elicit cell growth in the RD subline of RBS. RD cells were treated with different concentrations of PFOA. Cell proliferation was evaluated using Cell Counting Kit-8 and cell cycle assays. Cell migration and invasion were determined using wound healing and Transwell assays. Apoptotic rates were estimated by Annexin V-FITC/propidium iodide staining. The expression levels of vimentin, serum/glucocorticoid-regulated kinase 1 (SGK1), cyclin E2, cyclin dependent kinase (CDK)2, p53, p21, p27, phosphatidylinositol-3 kinase (PI3K) and protein kinase B (AKT), and apoptosis-associated genes and proteins (including Bcl-2 and Bax) were detected by reverse transcription-PCR and western blot analyses. The results showed that PFOA significantly promoted RD cell proliferation, migration and invasion and significantly inhibited RD cell apoptosis. Exposure to PFOA also induced the expression of vimentin, SGK1, cyclin E2, CDK2, AKT, PI3K and Bcl-2, but suppressed the expression of Bax in the RD cells. The treatment of RD cells with BEZ235, a PI3K inhibitor, antagonized the effects of PFOA on metastatic formation and apoptosis. The results obtained show that the PI3K/AKT signaling pathway is implicated in mediating the pro-neoplastic effects of PFOA. The data suggests that PFOA is a carcinogen capable of promoting RD cell migration and invasion and inhibiting apoptosis through the PI3K/AKT signaling pathway.

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Perfluorooctanoic acid (PFOA) exposure promotes proliferation, migration and invasion potential in human breast epithelial cells

Cited by 97 publications

References 57 publications

Perfluorinated alkylated substances serum concentration and breast cancer risk: Evidence from a nested case‐control study in the French E3N cohort

Perfluorinated alkylated substances serum concentration and breast cancer risk: Evidence from a nested case‐control study in the French E3N cohort

Application of the Key Characteristics of Carcinogens to Per and Polyfluoroalkyl Substances

Perfluorooctanoic acid induces migration and invasion and inhibits apoptosis through the PI3K/AKT signaling pathway in human rhabdomyosarcoma cells

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