{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T09:51:11Z","timestamp":1771494671432,"version":"3.50.1"},"reference-count":29,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T00:00:00Z","timestamp":1607299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003360","name":"Ligue Genevoise Contre le Cancer","doi-asserted-by":"publisher","award":["1515"],"award-info":[{"award-number":["1515"]}],"id":[{"id":"10.13039\/501100003360","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Genomic instability is generally considered as a hallmark of tumorigenesis and a prerequisite condition for malignant transformation. Aluminium salts are suspected environmental carcinogens that transform mammary epithelial cells in vitro through unknown mechanisms. We report here that long-term culture in the presence of aluminium chloride (AlCl3) enables HC11 normal mouse mammary epithelial cells to form tumours and metastases when injected into the syngeneic and immunocompetent BALB\/cByJ strain. We demonstrate that AlCl3 rapidly increases chromosomal structural abnormalities in mammary epithelial cells, while we failed to detect direct modulation of specific mRNA pathways. Our observations provide evidence that clastogenic activity\u2014a well-recognized inducer of genomic instability\u2014might account in part for the transforming abilities of aluminium in mammary epithelial cells.<\/jats:p>","DOI":"10.3390\/ijms21239332","type":"journal-article","created":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T21:37:42Z","timestamp":1607377062000},"page":"9332","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Genomic Instability Is an Early Event in Aluminium-Induced Tumorigenesis"],"prefix":"10.3390","volume":"21","author":[{"given":"Stefano J.","family":"Mandriota","sequence":"first","affiliation":[{"name":"Laboratoire de Canc\u00e9rogen\u00e8se Environnementale, Fondation des Grangettes, 1224 Ch\u00eane-Bougeries, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirna","family":"Tenan","sequence":"additional","affiliation":[{"name":"Laboratoire de Canc\u00e9rogen\u00e8se Environnementale, Fondation des Grangettes, 1224 Ch\u00eane-Bougeries, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4616-3599","authenticated-orcid":false,"given":"Adeline","family":"Nicolle","sequence":"additional","affiliation":[{"name":"Laboratoire de Canc\u00e9rogen\u00e8se Environnementale, Fondation des Grangettes, 1224 Ch\u00eane-Bougeries, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia D.","family":"Jankowska","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Laboratoire de Canc\u00e9rogen\u00e8se Environnementale, Fondation des Grangettes, 1224 Ch\u00eane-Bougeries, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2255-5918","authenticated-orcid":false,"given":"Jean-Christophe","family":"Tille","sequence":"additional","affiliation":[{"name":"Department of Pathology, Geneva University Hospital, 1205 Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4073-3463","authenticated-orcid":false,"given":"Mary-Anne","family":"Durin","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine M.","family":"Green","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1917-1729","authenticated-orcid":false,"given":"Sebastien","family":"Tabruyn","sequence":"additional","affiliation":[{"name":"TransCure bioServices, 74160 Archamps, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7977-8496","authenticated-orcid":false,"given":"Daniela","family":"Moralli","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9-Pascal","family":"Sappino","sequence":"additional","affiliation":[{"name":"Laboratoire de Canc\u00e9rogen\u00e8se Environnementale, Fondation des Grangettes, 1224 Ch\u00eane-Bougeries, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1097\/00008469-200110000-00002","article-title":"Underarm cosmetics are a cause of breast cancer","volume":"10","author":"Darbre","year":"2001","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S1470-2045(00)00254-0","article-title":"Epidemiology of breast cancer","volume":"3","author":"Key","year":"2001","journal-title":"Lancet Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1126\/science.1088759","article-title":"Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2","volume":"302","author":"King","year":"2003","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1097\/00008469-200312000-00006","article-title":"An earlier age of breast cancer diagnosis related to more frequent use of antiperspirants\/deodorants and underarm shaving","volume":"12","author":"McGrath","year":"2003","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.ebiom.2017.06.005","article-title":"Use of Underarm Cosmetic Products in Relation to Risk of Breast Cancer: A Case-Control Study","volume":"21","author":"Linhart","year":"2017","journal-title":"EBioMedicine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.morpho.2016.02.001","article-title":"Aluminium and the human breast","volume":"100","author":"Darbre","year":"2016","journal-title":"Morphologie"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/jat.1793","article-title":"Aluminium chloride promotes anchorage-independent growth in human mammary epithelial cells","volume":"32","author":"Sappino","year":"2012","journal-title":"J. Appl. Toxicol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2781","DOI":"10.1002\/ijc.30393","article-title":"Aluminium chloride promotes tumorigenesis and metastasis in normal murine mammary gland epithelial cells","volume":"139","author":"Mandriota","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.jinorgbio.2013.07.004","article-title":"Effect of aluminium on migratory and invasive properties of MCF-7 human breast cancer cells in culture","volume":"128","author":"Darbre","year":"2013","journal-title":"J. Inorg. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.jinorgbio.2015.09.001","article-title":"Effect of aluminium on migration of oestrogen unresponsive MDA-MB-231 human breast cancer cells in culture","volume":"152","author":"Bakir","year":"2015","journal-title":"J. Inorg. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.mrgentox.2012.07.007","article-title":"Comparative genotoxicity of aluminium and cadmium in embryonic zebrafish cells","volume":"750","author":"Pereira","year":"2013","journal-title":"Mutat. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1111\/tpj.14231","article-title":"A multi-level response to DNA damage induced by aluminium","volume":"98","author":"Chen","year":"2019","journal-title":"Plant J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1002\/j.1460-2075.1988.tb03048.x","article-title":"Prolactin regulation of beta-casein gene expression and of a cytosolic 120-kd protein in a cloned mouse mammary epithelial cell line","volume":"7","author":"Ball","year":"1988","journal-title":"EMBO J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5708","DOI":"10.1073\/pnas.1505979112","article-title":"Alternative to the soft-agar assay that permits high-throughput drug and genetic screens for cellular transformation","volume":"112","author":"Rotem","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/cbdd.12176","article-title":"Inhibitors of apoptotic proteins: New targets for anticancer therapy","volume":"82","author":"Saleem","year":"2013","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S12","DOI":"10.1007\/s12105-013-0462-z","article-title":"Fusion oncogenes in salivary gland tumors: Molecular and clinical consequences","volume":"7","author":"Stenman","year":"2013","journal-title":"Head Neck Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.ccell.2016.05.005","article-title":"YAP\/TAZ at the Roots of Cancer","volume":"29","author":"Zanconato","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1111\/j.1749-6632.1993.tb17195.x","article-title":"Growth suppression of normal mammary epithelial cells by wild-type p53","volume":"698","author":"Merlo","year":"1993","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1002\/jcp.24229","article-title":"p53 regulates epithelial-mesenchymal transition induced by transforming growth factor \u03b2","volume":"228","author":"Tan","year":"2013","journal-title":"J. Cell Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1016\/j.freeradbiomed.2007.07.010","article-title":"Aluminum: A potential pro-oxidant in sunscreens\/sunblocks?","volume":"43","author":"Nicholson","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1146\/annurev-pharmtox-010818-021031","article-title":"Metals and Mechanisms of Carcinogenesis","volume":"59","author":"Chen","year":"2019","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_22","first-page":"653","article-title":"The Health Effects of Aluminum Exposure","volume":"114","author":"Klotz","year":"2017","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5459","DOI":"10.1038\/sj.onc.1204709","article-title":"Mammary glands reconstituted with Neu\/ErbB2 transformed HC11 cells provide a novel orthotopic tumor model for testing anti-cancer agents","volume":"20","author":"Brandt","year":"2001","journal-title":"Oncogene"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1016\/j.biopha.2017.03.017","article-title":"Sulfatase-2 promotes the growth and metastasis of colorectal cancer by activating Akt and Erk1\/2 pathways","volume":"89","author":"Tao","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1158\/0008-5472.CAN-15-2556","article-title":"Transcriptional Induction of Periostin by a Sulfatase 2-TGF\u03b21-SMAD Signaling Axis Mediates Tumor Angiogenesis in Hepatocellular Carcinoma","volume":"77","author":"Chen","year":"2017","journal-title":"Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"16090","DOI":"10.18632\/oncotarget.7449","article-title":"Involvement of SULF2 in y-irradiation-induced invasion and resistance of cancer cells by inducing IL-6 expression","volume":"7","author":"Jung","year":"2016","journal-title":"Oncotarget"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1177\/0023677216640706","article-title":"A less invasive method for orthotopic injection of breast cancer cells into the mouse mammary gland","volume":"51","author":"Brown","year":"2017","journal-title":"Lab. Anim."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5406","DOI":"10.1038\/s41467-018-07855-x","article-title":"The ASCIZ-DYNLL1 axis promotes 53BP1-dependent non-homologous end joining and PARP inhibitor sensitivity","volume":"9","author":"Becker","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_29","first-page":"175","article-title":"ImageJ macros for the user-friendly analysis of soft-agar and wound-healing assays","volume":"32","year":"2017","journal-title":"Biotechniques"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/23\/9332\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:42:08Z","timestamp":1760179328000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/23\/9332"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,7]]},"references-count":29,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["ijms21239332"],"URL":"https:\/\/doi.org\/10.3390\/ijms21239332","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,7]]}}}