CoChat
Sign Up
Cited by 154Per- and polyfluoroalkyl substances researchEffects and risks of endocrine disrupting chemicalsEstrogen and related hormone effects

Estrogen-like properties of fluorotelomer alcohols as revealed by MCF-7 breast cancer cell proliferation

Open access
Maras, Marleen, Vanparys, Caroline, Muylle, Frederik, Robbens, Johan, Berger, Urs, Barber, Jonathan L., Blust, Ronny, De Coen, Wim·2006·Environmental Health Perspectives
DOI 10.1289/ehp.8149PMC PMC1332663
Open this paper in CoChat — free account

Abstract

We investigated estrogen-like properties of five perfluorinated compounds using a combination of three in vitro assays. By means of an E-screen assay, we detected the proliferation-promoting capacity of the fluorotelomer alcohols 1H,1H,2H,2H-perfluorooctan-1-ol (6:2 FTOH) and 1H,1H,2H,2H-perfluoro-decan-1-ol (8:2 FTOH). The more widely environmentally distributed compounds perfluoro-1-octane sulfonate, perfluorooctanoic acid, and perfluorononanoic acid did not seem to possess this hormone-dependent proliferation capacity. We investigated cell cycle dynamics using flow cytometric analyses of the DNA content of the nuclei of MCF-7 breast cancer cells. Exposure to both fluorotelomer alcohols stimulated resting MCF-7 cells to reenter the synthesis phase (S-phase) of the cell cycle. After only 24 hr of treatment, we observed significant increases in the percentage of cells in the S-phase. In order to further investigate the resemblance of the newly detected xenoestrogens to the reference compound 17β-estradiol (E2), gene expression of a number of estrogen-responsive genes was analyzed by real-time polymerase chain reaction. With E2, as well as 4-nonylphenol and the fluorotelomer alcohols, we observed up-regulation of trefoil factor 1, progesterone receptor, and PDZK1 and down-regulation of ERBB2 gene expression. We observed small but relevant up-regulation of the estrogen receptor as a consequence of exposures to 6:2 FTOH or 8:2 FTOH. The latter finding suggests an alternative mode of action of the fluorotelomer alcohols compared with that of E2. This study clearly underlines the need for future in vivo testing for specific endocrine-related end points.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1289/ehp.8149

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • FTOHs can cause endocrine disruption to fish and human cells and reproductive damage in fish and rats.

    “A growing number of studies have shown that FTOHs can cause endocrine disruption to fish and human cells and reproductive damage in fish and rats (Liu et al., 2010a; Maras et al., 2006).”

    From Biotransformation of perfluoroalkyl acid precursors from various environmental systems: advances and perspectives (2021) · cites this paper as Maras et al., 2006

    The Discussion reports that 6:2 and 8:2 FTOH showed estrogen-like activity in human MCF-7 cells in vitro. It does not establish endocrine disruption or reproductive damage in fish. For rats, the Discussion instead cites a reproductive toxicity study that found no harmful effect on reproduction. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • 6:2 and 8:2 FTOH have estrogen-like effects.

    “while cell proliferation experiments have shown that 6:2 and 8:2 FTOH have estrogen-like effects (Maras et al., 2006).”

    From Biotransformation of perfluoroalkyl acid precursors from various environmental systems: advances and perspectives (2021) · cites this paper as Maras et al., 2006

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 43

  1. Austin ME Kasturi BS Barber M Kannan K MohanKumar PS MohanKumar SMJ 2003 Neuroendocrine effects of per-fluorooctane sulfonate in rats Environ Health Perspect 111 1485 1489 12948888 PMC1241651
  2. Bièche I Parfait B Le Doussal V Olivi M Rio M Lidereau R 2001 Identification of CGA as a novel estrogen receptor-responsive gene in breast cancer: an outstanding candidate marker to predict the response to endocrine therapy Cancer Res 61 1652 1658 11245479
  3. Coser KR Chesnes J Hur J Ray S Isselbacher KJ Shioda T 2003 Global analysis of ligand sensitivity of estrogen inducible and suppressible genes in MCF7/BUS breast cancer cells by DNA microarray Proc Nat Acad Sci USA 100 13994 13999 14610279 PMC283534
  4. Degen GH Bolt HM 2000 Endocrine disruptors: update on xenoestrogens Int Arch Occup Environ Health 73 433 441 11057411
  5. Dimitrov S Kamenska V Walker JD Windle W Purdy R Lewis M 2004 Predicting the biodegradation products of perfluorinated chemicals using CATABOL SAR QSAR Environ Res 15 69 82 15113070
  6. Dinglasan MJA Ye Y Edwards EA Mabury SA 2004 Fluorotelomer alcohols yields poly-and perfluorinated acids Environ Sci Technol 38 2857 2864 15212260
  7. Frasor J Danes JM Komm B Chang KNC Lyttle R Katzenellenbogen BS 2003 Profiling of estrogen up- and down-regulated gene expression in human breast cancer cells: insights into gene networks and pathways underlying estrogenic control of proliferation and cell phenotype Endocrinology 144 4562 4574 12959972
  8. GenBank 2005. Searching GenBank. Bethesda, MD:National Center for Biotechnology Information, U.S. National Library of Medicine. Available: http://www.ncbi.nlm.nih.gov/Genbank/GenbankSearch.html [accessed 2 April 2005].
  9. Ghosh MG Thompson DA Weigel RJ 2000 PDZK1 and GREB1 are estrogen-regulated genes expressed in hormone-responsive breast cancer Cancer Res 60 6367 6375 11103799
  10. Giesy JP Kannan K Jones PD 2001 Global biomonitoring of perfluorinated organics Sci World J 1 627 629 PMC6084175 12805763
  11. Hoff PT Van de Vijver K Van Dongen W Esmans EL Blust R De Coen WM 2003a Perfluorooctane sulfonic acid in bib (Trisopteris luscus) and plaice (Pleuronectes platessa) from the Western Scheldt and the Belgian North Sea: distribution and biochemical effects Environ Toxicol Chem 22 608 614 12627649
  12. Hoff PT Van Dongen W Esmans EL Blust R De Coen WM 2003b Evaluation of the toxicological effects of perfluorooctane sulfonic acid in the common carp (Cyprinus carpio) Aquat Toxicol 62 349 359 12595174
  13. Inoue A Yoshida N Omoto Y Oguchi S Yamori T Kiyama R 2002 Development of cDNA microarray for expression profiling of estrogen-responsive genes J Mol Endocrinol 29 175 192 12370120
  14. Jones LJ Gray M Yue ST Haugland RP Singer VL 2001 Sensitive determination of cell number using the CyQuant cell proliferation assay J Immunol Methods 254 85 98 11406155
  15. Jorgensen M Vendelbo B Skakkebaek NE Leffers H 2000 Assaying estrogenicity by quantitating the expression levels of endogenous estrogen-regulated genes Environ Health Perspect 108 403 412 10811566 PMC1638061
  16. Katzenellenbogen BS 1995 The structural pervasiveness of estrogenic activity Environ Health Perspect 103 suppl 7 99 101 8593885 PMC1518874
  17. Kraus WL Weis KE Katzenellenbogen BS 1995 Inhibitory cross-talk between steroid hormone receptors: differential targeting of estrogen receptor in the repression of its transcriptional activity by agonist- and antagonist-occupied progestin receptors Mol Cell Biol 15 1847 1857 7891678 PMC230410
  18. Kraus WL Weis KE Katzenellenbogen BS 1997 Determinants for the repression of estrogen receptor transcriptional activity by ligand-occupied progestin receptors J Steroid Biochem Mol Biol 63 175 188 9459183
  19. Ladics GS Stadler JC Makovec GT Everds NE Buck RC 2005 Subchronic toxicity of a fluoroethylalkanol mixture in rats Drug Chem Toxicol 28 135 158 15865257
  20. Lange CA Richer JK Horwitz KB 2005 Hypothesis: progesterone primes breast cancer cells for cross-talk with proliferative or antiproliferative signals Mol Endocrinol 13 829 835 10379882
  21. Lau C Butenhoff JL Rogers JM 2004 The developmental toxicity of perfluoroalkyl acids and their derivatives Toxicol Appl Pharmacol 198 231 241 15236955
  22. Lehmler H 2005 Synthesis of environmentally relevant fluorinated surfactants—a review Chemosphere 58 1471 1496 15694468
  23. Martin JW Smithwick MM Braune BM Hoekstra PF Muir DC Marbury SA 2004 Identification of long-chain perfluorinated acids in biota from the Canadian Arctic Environ Sci Technol 38 373 380 14750710
  24. Mylchreest E Ladics GS Munley SM Buck RC Stadler JC 2005 Evaluation of the reproductive and developmental toxicity of a fluoroalkylethanol mixture Drug Chem Toxicol 28 159 175 15865258
  25. Olsen CM Meussen-Elholm ETM Samuelsen M Holme JA Hongslo JK 2003 Effects of the environmental oestrogens bisphenol A, tetrachlorobisphenol A, tetrabromobisphenol A, 4-hydroxybiphenyl and 4,4’-dihydroxybiphenyl on oestrogen receptor binding, cell proliferation and regulation of oestrogen sensitive proteins in the human breast cancer cell line MCF-7 Pharmacol Toxicol 92 180 188 12753421
  26. Payne J Jones C Lakhani S Kortenkamp A 2000 Improving the reproducibility for the detection of xenoestrogens Sci Total Environ 248 51 62 10807042
  27. Pfaffl MW Horgan GW Dempfle L 2002 Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR Nucleic Acids Res 30 e36 11972351 PMC113859
  28. Renner R 2001 Growing concerns over perfluorinated compounds Environ Sci Technol 35 154A 160A 11348100
  29. Renner R 2003 Concerns over common perfluorinated surfactants Environ Sci Technol 37 201A 202A 12831000
  30. Rosselli M Reinhart K Imthurn B Keller PJ Dubey RK 2000 Cellular and biochemical mechanisms by which environmental oestrogens influence reproductive function Hum Reprod Update 6 332 350 10972521
  31. Sargent JW Seffl RJ 1970 Properties of perfluorinated liquids Fed Proc 29 1699 1703 5457573
  32. Schantz SL Widholm JJ 2001 Cognitive effects of endocrine-disrupting chemicals in animals Environ Health Perspect 109 1197 1206 11748026 PMC1240501
  33. Soto AM Sonnenschein C Chung KL Fernandez MF Olea N Olea Serrano F 1995 The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants Environ Health Perspect 103 suppl 7 113 122 8593856 PMC1518887
  34. Tabira Y Nakai M Asai D Yakabe Y Tahara Y Shinmyozu T 1999 Structural requirements of para-alkylphenols to bind to estrogen receptor Eur J Biochem 262 240 245 10231387
  35. Terasaka S Aita Y Inoue A Hayashi S Nishigaki M Aoyagi K 2004 Using a customized DNA microarray for expression profiling of the estrogen-responsive genes to evaluate estrogen activity among natural estrogens and industrial chemicals Environ Health Perspect 112 773 781 15159206 PMC1241992
  36. Yang N Higuchi O Mizuno K 1998 Cytoplasmic localization of LIM-kinase 1 is directed by a short sequence within the PDZ domain Exp Cell Res 241 242 252 9633533
  37. Yoshida N Omoto Y Inoue A Eguchi H Kobayashi Y Kurosumi M 2004 Prediction of prognosis of estrogen receptor-positive breast cancer with combination of selected estrogen-regulated genes Cancer Sci 95 496 502 15182430 PMC11158785
  38. Van de Vijver KI Hoff PT Das K Van Dongen W Esmans EL Siebert U 2004 Baseline study of perfluorochemicals in harbour porpoises (Phocoena phocoena) from Northern Europe Mar Pollut Bull 48 992 997 15111049
  39. Van de Vijver KI Hoff PT Van Dongen W Blust R De Coen WM 2003 Perfluorinated chemicals infiltrate ocean waters: link between exposure levels and stable isotope ratios in marine mammals Environ Sci Toxicol Chem 22 2037 2041 14717162
  40. Vendrell JA Magnino F Danis E Duchesne MJ Pinloche S Pons M 2004 Estrogen regulation in human breast cancer cells of new downstream gene targets involved in estrogen metabolism, cell proliferation and cell transformation J Mol Endocrinol 32 397 414 15072547
  41. Villalobos M Olea N Brotons JA Olea-Serrano MF Ruiz de Almodovar JM Pedraza V 1995 The E-screen assay: a comparison of different MCF7 cell stocks Environ Health Perspect 103 844 850 7498097 PMC1519213
  42. Vindelov LL Christensen IJ Nissen NI 1983 A detergent-trypsin method for the preparation of nuclei for flow cytometric DNA analysis Cytometry 3 323 327 6188586
  43. Wang Z Lou Y 2004 Proliferation-stimulating effects of icaritin and desmethylicaritin in MCF-7 cells Eur J Pharmacol 504 147 153 15541416

Cited by

Sorted by citations

Authors
Maras, M., Vanparys, C., Muylle, F., Robbens, J., Berger, U., Barber, J. L., Blust, R., & De Coen, W.
Affiliations
  • University of Antwerp (BE)
  • NILU (NO)
  • Lancaster University (GB)
  • Laboratory for Ecophysiology, Biochemistry, and Toxicology, University of Antwerp, Antwerp, Belgium
ORCID
Venue
Environmental Health Perspectives
Publisher
American Chemical Society (ACS)
Published
2005-09-01
Volume
114
Issue
1
Pages
100-105
ISSN
  • 0091-6765 (ISSN-L)
  • 1552-9924
DOI
10.1289/ehp.8149
PMC
PMC1332663
OpenAlex
W1966632247
Cited by
154
References
0
Citations by year
2026: 3 · 2025: 7 · 2024: 6 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 6 · 2018: 4 · 2017: 5 · 2016: 10 · 2015: 10 · 2014: 10 · 2013: 6 · 2012: 3
FWCI
8.52
Type
journal article
Language
en
Open access
Licence
Locations
  • Environmental Health Perspectives (publishedVersion, public-domain)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • Lancaster EPrints (Lancaster University) (submittedVersion)
Topics
  • Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
fluorotelomer alcohols, perfluorinated compounds, xenoestrogens, estrogenic activity, MCF-7 cells, perfluorooctanoic acid, PFOS, perfluorononanoic acid, cell cycle, S phase entry, estrogen receptor, estrogen-responsive gene expression, 4-nonylphenol, endocrine disruptors
MeSH terms
Trefoil Factor-1, Breast Neoplasms, Carrier Proteins, Cell Cycle, Estrogens, Fluorocarbons, Gene Expression Regulation, Humans, Membrane Proteins, Receptors, Progesterone, RNA, Messenger, Erb-b2 Receptor Tyrosine Kinases, Receptor, ErbB-2, Reverse Transcriptase Polymerase Chain Reaction, Tumor Suppressor Proteins, Cell Line, Tumor, Estrogen Receptor alpha, Cell Proliferation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review