The endocrine disruptor cadmium modulates the androgen-estrogen receptors ratio and induces inflammatory cytokines in luminal (A) cell models of breast cancer.

التفاصيل البيبلوغرافية
العنوان:	The endocrine disruptor cadmium modulates the androgen-estrogen receptors ratio and induces inflammatory cytokines in luminal (A) cell models of breast cancer.
المؤلفون:	Bimonte VM; Department of Movement, Human and Health Sciences, University of Foro Italico, 00195, Rome, Italy., Catanzaro G; Department of Experimental Medicine, 'Sapienza' University of Rome, 00161, Rome, Italy., Po A; Department of Molecular Medicine, 'Sapienza' University of Rome, 00161, Rome, Italy., Trocchianesi S; Department of Molecular Medicine, 'Sapienza' University of Rome, 00161, Rome, Italy., Besharat ZM; Department of Experimental Medicine, 'Sapienza' University of Rome, 00161, Rome, Italy., Spinello Z; Department of Experimental Medicine, 'Sapienza' University of Rome, 00161, Rome, Italy., Curreli M; Department of Movement, Human and Health Sciences, University of Foro Italico, 00195, Rome, Italy., Fabi A; Precision Medicine in Senology Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168, Rome, Italy., Bei R; Department of Clinical Sciences and Translational Medicine, University of Rome 'Tor Vergata', 00133, Rome, Italy., Milella M; Department of Oncology, University of Verona, 37134, Verona, Italy., Vacca A; Department of Experimental Medicine, 'Sapienza' University of Rome, 00161, Rome, Italy., Ferretti E; Department of Experimental Medicine, 'Sapienza' University of Rome, 00161, Rome, Italy., Migliaccio S; Department of Movement, Human and Health Sciences, University of Foro Italico, 00195, Rome, Italy. silvia.migliaccio@uniroma4.it.
المصدر:	Endocrine [Endocrine] 2024 Mar; Vol. 83 (3), pp. 798-809. Date of Electronic Publication: 2023 Nov 18.
نوع المنشور:	Journal Article
اللغة:	English
بيانات الدورية:	Publisher: Humana Press Country of Publication: United States NLM ID: 9434444 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-0100 (Electronic) Linking ISSN: 1355008X NLM ISO Abbreviation: Endocrine Subsets: MEDLINE
أسماء مطبوعة:	Publication: Feb. 1996- : Totowa, NJ : Humana Press Original Publication: Houndsmills, Basingstoke, Hants, UK : Macmillan Press, c1994-
مواضيع طبية MeSH:	Breast Neoplasms/pathology , Endocrine Disruptors/pharmacology, Female ; Humans ; Cadmium/toxicity ; Androgens/pharmacology ; Receptors, Androgen/metabolism ; Receptors, Estrogen/metabolism ; Cytokines ; Estrogens ; Interleukin-6 ; Cell Line, Tumor ; Tumor Microenvironment
مستخلص:	Purpose: Breast cancer (BC) is the most common malignancy that affects women, and it is, to date, their leading cause of death. Luminal A molecular subtype accounts for 40% of BC and is characterized by hormone receptors positive/human epidermal growth factor 2 expression and current treatment consists of surgery plus aromatase inhibitor therapy. Interestingly, several studies demonstrated that the heavy metal cadmium (Cd), classified as a group 1 human carcinogen and widely spread in the environment, exerts estrogen-like activities in several tissues and suggested an intriguing relationship between increased Cd exposure and BC incidence. Thus, aim of this study was to evaluate effects of Cd on Luminal A BC estrogen receptor (ER) positive/progesterone receptor positive cell models in vitro to characterize the mechanism(s) involved in breast cell homeostasis disruption. Methods: T47D and MCF7 were exposed to Cd (0.5-1 µM) for 6-24 h to evaluate potential alterations in: cells viability, steroid receptors and intracellular signaling by western blot. Moreover, we evaluated the expression of inflammatory cytokines interleukin by RT-PCR. Results: Our results showed a significant induction of androgen receptor (AR) and an increased AR/ER ratio. Further, Cd exposure increased pro-inflammatory cytokines interleukin (IL)6, IL8 and tumor necrosis factor α levels. Finally, as previously demonstrated by our group, Cd alters pathways such as mitogen-activated protein kinase family and protein kinase B. Conclusion: In conclusion, our study demonstrates that Cd modifies the expression and pattern of ERs and AR in BC cell lines, suggesting an alteration of BC cells homeostasis, likely predisposing to a carcinogenetic microenvironment. (© 2023. The Author(s).)
References:	D. Trapani, O. Ginsburg, T. Fadelu, N.U. Lin, M. Hassett, A.M. Ilbawi, B.O. Anderson, G. Curigliano, Global challenges and policy solutions in breast cancer control. Cancer Treat. Rev. 104, 102339 (2022). (PMID: 3507472710.1016/j.ctrv.2022.102339) B. Starek-Świechowicz, B. Budziszewska, A. Starek, Endogenous estrogens—breast cancer and chemoprevention. Pharmacol. Rep. 73, 1497–1512 (2021). (PMID: 34462889859925610.1007/s43440-021-00317-0) P. Yaşar, G. Ayaz, S.D. User, G. Güpür, M. Muyan, Molecular mechanism of estrogen–estrogen receptor signaling. Reprod. Med. Biol. 16, 4–20 (2017). (PMID: 2925944510.1002/rmb2.12006) S. Migliaccio, M. Marino, Estrogens and estrogen receptors: new actors in the plot of transcriptional regulation of genomic responses. Calcif. Tissue Int. 72, 181 (2003). (PMID: 1252266610.1007/s00223-002-1042-5) P. Ascenzi, A. Bocedi, M. Marino, Structure–function relationship of estrogen receptor Α and Β: impact on human health. Mol. Asp. Med. 27, 299–402 (2006). (PMID: 10.1016/j.mam.2006.07.001) M. Longo, M. Brama, M. Marino, S. Bernardini, K.S. Korach, W.C. Wetsel, R. Scandurra, T. Faraggiana, G. Spera, R. Baron, Interaction of estrogen receptor Α with protein kinase C Α and C-Src in osteoblasts during differentiation. Bone 34, 100–111 (2004). (PMID: 1475156710.1016/j.bone.2003.09.007) A.R. Dwyer, T.H. Truong, J.H. Ostrander, C.A. Lange, 90 years of progesterone: steroid receptors as MAPK signaling sensors in breast cancer: let the fates decide. J. Mol. Endocrinol. 65, T35–T48 (2020). (PMID: 32209723732958410.1530/JME-19-0274) M. Hirao-Suzuki, Estrogen receptor Β as a possible double-edged sword molecule in breast cancer: a mechanism of alteration of its role by exposure to endocrine-disrupting chemicals. Biol. Pharm. Bull. 44, 1594–1597 (2021). (PMID: 3471963710.1248/bpb.b21-00468) I. Nita, C. Nitipir, S.A. Toma, A.M. Limbau, E. Pirvu, I.A. Badarau, The importance of androgen receptors in breast cancer. Med. Pharm. Rep. 94, 273–281 (2021). (PMID: 344308488357358) M. Fiocchetti, G. Bastari, M. Cipolletti, S. Leone, F. Acconcia, M. Marino, The peculiar estrogenicity of diethyl phthalate: modulation of estrogen receptor Α activities in the proliferation of breast cancer cells. Toxics 9, 237 (2021). (PMID: 34678933853867410.3390/toxics9100237) P.D. Darbre, Endocrine disrupting chemicals and breast cancer cells. Adv. Pharmacol. 92, 485–520 (2021). (PMID: 3445269510.1016/bs.apha.2021.04.006) J. Luevano, C. Damodaran, A review of molecular events of cadmium-induced carcinogenesis. J. Environ. Pathol. Toxicol. Oncol. 33, 183–194 (2014). (PMID: 25272057418396410.1615/JEnvironPatholToxicolOncol.2014011075) C. Byrne, S.D. Divekar, G.B. Storchan, D.A. Parodi, M.B. Martin, Cadmium—a metallohormone? Toxicol. Appl. Pharmacol. 238, 266–271 (2009). (PMID: 19362102270971110.1016/j.taap.2009.03.025) L. Strumylaite, A. Bogusevicius, O. Abdrachmanovas, D. Baranauskiene, R. Kregzdyte, D. Pranys, L. Poskiene, Cadmium concentration in biological media of breast cancer patients. Breast Cancer Res. Treat. 125, 511–517 (2011). (PMID: 2060760210.1007/s10549-010-1007-8) P. Joseph, Mechanisms of cadmium carcinogenesis. Toxicol. Appl. Pharmacol. 238, 272–279 (2009). (PMID: 1937161710.1016/j.taap.2009.01.011) M.P. Waalkes, Cadmium carcinogenesis. Mutat. Res. - Fundam. Mol. Mech. Mutagen. 533, 107–120 (2003). (PMID: 10.1016/j.mrfmmm.2003.07.011) K. Tarhonska, M. Lesicka, B. Janasik, J. Roszak, E. Reszka, M. Braun, A. Kołacińska-Wow, E. Jabłońska, Cadmium and breast cancer–current state and research gaps in the underlying mechanisms. Toxicol. Lett. 361, 29–42 (2022). (PMID: 3533184010.1016/j.toxlet.2022.03.003) M. Brama, L. Gnessi, S. Basciani, N. Cerulli, L. Politi, G. Spera, S. Mariani, S. Cherubini, A.S. d’Abusco, R. Scandurra, Cadmium induces mitogenic signaling in breast cancer cell by an ERα-dependent mechanism. Mol. Cell. Endocrinol. 264, 102–108 (2007). (PMID: 1712591310.1016/j.mce.2006.10.013) P. Garcia-Morales, M. Saceda, N. Kenney, N. Kim, D.S. Salomon, M.M. Gottardis, H.B. Solomon, P.F. Sholler, V.C. Jordan, M.B. Martin, Effect of cadmium on estrogen receptor levels and estrogen-induced responses in human breast. Cancer Cells J. Biol. Chem. 269, 16896–16901 (1994). (PMID: 8207012) A. Stoica, B.S. Katzenellenbogen, M.B. Martin, Activation of estrogen receptor-Α by the heavy metal cadmium. Mol. Endocrinol. 14, 545–553 (2000). (PMID: 10770491) W.V. Welshons, M.F. Wolf, C.S. Murphy, V.C. Jordan, Estrogenic activity of phenol red. Mol. Cell. Endocrinol. 57, 169–178 (1988). (PMID: 340266010.1016/0303-7207(88)90072-X) V. Papa, V. Bimonte, F. Wannenes, A. D’Abusco, S. Fittipaldi, R. Scandurra, L. Politi, C. Crescioli, A. Lenzi, L. Di Luigi, The endocrine disruptor cadmium alters human osteoblast-like Saos-2 cells homeostasis in vitro by alteration of Wnt/Β-catenin pathway and activation of caspases. J. Endocrinol. Invest. 38, 1345–1356 (2015). (PMID: 2633530110.1007/s40618-015-0380-x) V.M. Bimonte, F. Marampon, A. Antonioni, S. Fittipaldi, E. Ferretti, R.G. Pestell, M. Curreli, A. Lenzi, G. Vitale, A. Brunetti, Phosphodiesterase type-5 inhibitor tadalafil modulates steroid hormones signaling in a prostate cancer cell line. Int. J. Mol. Sci. 22, 754 (2021). (PMID: 33451122782862810.3390/ijms22020754) A. Po, A. Citarella, G. Catanzaro, Z.M. Besharat, S. Trocchianesi, F. Gianno, C. Sabato, M. Moretti, E. De Smaele, A. Vacca, Hedgehog-GLI signalling promotes chemoresistance through the regulation of ABC transporters in colorectal cancer cells. Sci. Rep. 10, 13988 (2020). (PMID: 32814794743853110.1038/s41598-020-70871-9) V.M. Bimonte, S. Fittipaldi, C. Marocco, G.P. Emerenziani, R. Fornari, L. Guidetti, E. Poggiogalle, E. Nicolai, L. Di Luigi, L.M. Donini, Physical activity and hypocaloric diet recovers osteoblasts homeostasis in women affected by abdominal obesity. Endocrine 58, 340–348 (2017). (PMID: 2798151610.1007/s12020-016-1193-1) A.R. Michmerhuizen, D.E. Spratt, L.J. Pierce, C.W. Speers, ARe we there yet? Understanding androgen receptor signaling in breast cancer. NPJ breast cancer 6, 47 (2020). (PMID: 33062889751966610.1038/s41523-020-00190-9) A. Anestis, I. Zoi, A.G. Papavassiliou, M.V. Karamouzis, Androgen receptor in breast cancer—clinical and preclinical research insights. Molecules 25, 358 (2020). (PMID: 31952272702433010.3390/molecules25020358) S. Fittipaldi, V. Bimonte, A. Soricelli, A. Aversa, A. Lenzi, E. Greco, S. Migliaccio, Cadmium exposure alters steroid receptors and proinflammatory cytokine levels in endothelial cells in vitro: a potential mechanism of endocrine disruptor atherogenic. Eff. J. Endocrinol. Invest. 42, 727–739 (2019). (PMID: 10.1007/s40618-018-0982-1) E.H. Hassanein, W.R. Mohamed, O.S. Ahmed, M.M. Abdel-Daim, A.M. Sayed, The role of inflammation in cadmium nephrotoxicity: NF-κB comes into view. Life Sci. 308, 120971 (2022). (PMID: 3613061710.1016/j.lfs.2022.120971) O. Ostrovsky, I. Vlodavsky, A. Nagler, Mechanism of HPSE gene SNPs function: from normal processes to inflammation, cancerogenesis and tumor progression. Adv. Exp. Med. Biol. 1221, 231–249 (2020). (PMID: 3227471210.1007/978-3-030-34521-1_8) J.H. Ma, L. Qin, X. Li, Role of STAT3 signaling pathway in breast cancer. Cell. Commun. Signal. 18, 33 (2020). (PMID: 32111215704813110.1186/s12964-020-0527-z) R.A. Goyer, Toxic and essential metal interactions. Annu. Rev. Nutr. 17, 37–50 (1997). (PMID: 924091810.1146/annurev.nutr.17.1.37) M. Peana, A. Pelucelli, C.T. Chasapis, S.P. Perlepes, V. Bekiari, S. Medici, M.A. Zoroddu, Biological effects of human exposure to environmental cadmium. Biomolecules 13, 36 (2022). (PMID: 36671421985564110.3390/biom13010036) V.A. Flórez-García, E. Guevara-Romero, M. Hawkins, L.E. Bautista, T. Jenson, J. Yu, A. Kalkbrenner, Cadmium exposure and risk of breast cancer: a meta-analysis. Environ. Res. 219, 115109 (2023). (PMID: 3656398310.1016/j.envres.2022.115109) J.A. Aka, S.X. Lin, Comparison of functional proteomic analyses of human breast cancer cell lines T47D and MCF7. PLoS One 7, e31532 (2012). (PMID: 2238403510.1371/annotation/18f08a33-35e1-4bf9-8d21-476757dccbef) S. Yu, T. Kim, K.H. Yoo, K. Kang, The T47D cell line is an ideal experimental model to elucidate the progesterone-specific effects of a luminal A subtype of breast cancer. Biochem. Biophys. Res. Commun. 486, 752–758 (2017). (PMID: 2834286610.1016/j.bbrc.2017.03.114) K. Shen, H. Yu, B. Xie, Q. Meng, C. Dong, K. Shen, H. Zhou, Anticancer or carcinogenic? The role of estrogen receptor β in breast cancer progression. Pharmacol. Ther. 242, 108350 (2023). (PMID: 3669007910.1016/j.pharmthera.2023.108350) S.S. Elbalka, I.H. Metwally, A. Hassan, A.E. Eladl, A.M. Shoman, M. Jawad, E. Shahda, M. Abdelkhalek, Prognostic value of androgen receptor expression in different molecular types of breast cancer in women. Breast Dis. 41, 495–502 (2022). (PMID: 3664165610.3233/BD-220037) L. Tahtamouni, A. Alzghoul, S. Alderfer, J. Sun, M. Ahram, A. Prasad, J. Bamburg, The role of activated androgen receptor in cofilin phospho-regulation depends on the molecular subtype of TNBC cell line and actin assembly dynamics. Plos One 17, e0279746 (2022). (PMID: 36584207980330510.1371/journal.pone.0279746) C. You, H. Tsoi, E.P. Man, M. Leung, U. Khoo, Modulating the activity of androgen receptor for treating breast cancer. Int. J. Mol. Sci. 23, 15342 (2022). (PMID: 36499670973917810.3390/ijms232315342) V. Folgiero, S. Di Carlo, G. Bon, E. Spugnini, A. Di Benedetto, S. Germoni, M. Pia Gentileschi, A. Accardo, M. Milella, G. Morelli, Inhibition of p85, the non-catalytic subunit of phosphatidylinositol 3-kinase, exerts potent antitumor activity in human breast cancer cells. Cell Death Dis. 3, e440 (2012). (PMID: 23222510354261510.1038/cddis.2012.179) L.R. Gomes, L.F. Terra, R.A. Wailemann, L. Labriola, M.C. Sogayar, TGF-β1 modulates the homeostasis between MMPs and MMP inhibitors through p38 MAPK and ERK1/2 in highly invasive breast cancer cells. BMC Cancer 12, 26 (2012). (PMID: 22260435327746110.1186/1471-2407-12-26) M. Limoge, A. Safina, A.M. Truskinovsky, I. Aljahdali, J. Zonneville, A. Gruevski, C.L. Arteaga, A.V. Bakin, Tumor p38MAPK signaling enhances breast carcinoma vascularization and growth by promoting expression and deposition of pro-tumorigenic factors. Oncotarget 8, 61969–61981 (2017). (PMID: 28977919561747910.18632/oncotarget.18755) V.S. Sivaraman, H. Wang, G.J. Nuovo, C.C. Malbon, Hyperexpression of mitogen-activated protein kinase in human breast cancer. J. Clin. Investig. 99, 1478–1483 (1997). (PMID: 911999050796610.1172/JCI119309) H. Mueller, N. Flury, S. Eppenberger-Castori, W. Kueng, F. David, U. Eppenberger, Potential prognostic value of mitogen-activated protein kinase activity for disease-free survival of primary breast cancer patients. Int. J. Cancer 89, 384–388 (2000). (PMID: 1095641410.1002/1097-0215(20000720)89:4<384::AID-IJC11>3.0.CO;2-R) O. Habanjar, R. Bingula, C. Decombat, M. Diab-Assaf, F. Caldefie-Chezet, L. Delort, Crosstalk of inflammatory cytokines within the breast tumor microenvironment. Int. J. Mol. Sci. 24, 4002 (2023). (PMID: 36835413996471110.3390/ijms24044002) N. Todorović-Raković, J. Milovanović, Interleukin-8 in breast cancer progression. J. Interferon Cytokine Res. 33, 563–570 (2013). (PMID: 23697558379364710.1089/jir.2013.0023) H. Korkaya, G. Kim, A. Davis, F. Malik, N.L. Henry, S. Ithimakin, A.A. Quraishi, N. Tawakkol, R. D’Angelo, A.K. Paulson, S. Chung, T. Luther, H.J. Paholak, S. Liu, K.A. Hassan, Q. Zen, S.G. Clouthier, M.S. Wicha, Activation of an IL6 inflammatory loop mediates trastuzumab resistance in HER2+ breast cancer by expanding the cancer stem cell population. Mol. Cell 47, 570–584 (2012). (PMID: 22819326343241910.1016/j.molcel.2012.06.014) A.S. Ibrahim, M. El-Shinawi, S. Sabet, S.A. Ibrahim, M.M. Mohamed, RoLe Of Adipose Tissue-derived Cytokines In The Progression Of Inflammatory Breast Cancer In Patients With Obesity. Lipids health dis. 21, 1–13 (2022). (PMID: 10.1186/s12944-022-01678-y) A.K. Sasser, N.J. Sullivan, A.W. Studebaker, L.F. Hendey, A.E. Axel, B.M. Hall, Interleukin-6 is a potent growth factor for ER-alpha-positive human breast cancer. FASEB J. 21, 3763–3770 (2007). (PMID: 1758672710.1096/fj.07-8832com) D. Iliopoulos, H.A. Hirsch, G. Wang, K. Struhl, Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion. Proc. Natl Acad. Sci. USA 108, 1397–1402 (2011). (PMID: 21220315302976010.1073/pnas.1018898108) N.J. Sullivan, A.K. Sasser, A.E. Axel, F. Vesuna, V. Raman, N. Ramirez, T.M. Oberyszyn, B.M. Hall, Interleukin-6 induces an epithelial-mesenchymal transition phenotype in human breast cancer cells. Oncogene 28, 2940–2947 (2009). (PMID: 19581928557603110.1038/onc.2009.180) S.G. Manore, D.L. Doheny, G.L. Wong, H.W. Lo, IL-6/JAK/STAT3 signaling in breast cancer metastasis: biology and treatment. Front. Oncol. 12, 866014 (2022). (PMID: 35371975896497810.3389/fonc.2022.866014) M. Esquivel-Velázquez, P. Ostoa-Saloma, M.I. Palacios-Arreola, K.E. Nava-Castro, J.I. Castro, J. Morales-Montor, The role of cytokines in breast cancer development and progression. J. Interferon Cytokine Res. 35, 1–16 (2015). (PMID: 25068787429121810.1089/jir.2014.0026) I.H. Benoy, R. Salgado, P. Van Dam, K. Geboers, E. Van Marck, S. Scharpé, L.Y. Dirix, Increased serum interleukin-8 in patients with early and metastatic breast cancer correlates with early dissemination and survival. Clin. Cancer Res. 10, 7157–7162 (2004). (PMID: 1553408710.1158/1078-0432.CCR-04-0812) Q. Xie, Z.J. Yang, X.M. Huang, Z.K. Zhang, J.B. Li, J.H. Ju, H. Zhang, J.Y. Ma, Ilamycin C induces apoptosis and inhibits migration and invasion in triple-negative breast cancer by suppressing IL-6/STAT3 pathway. J. Hematol. Oncol. 12, 1 (2019). (PMID: 10.1186/s13045-019-0744-3) M.Z. Kamran, P. Patil, R.P. Gude, Role of STAT3 in cancer metastasis and translational advances. Biomed. Res. Int. 15, 421821 (2013). F. Zhang, G.D. Yin, X.F. Han, X.Q. Jiang, Z.S. Bao, Chlorogenic acid inhibits osteosarcoma carcinogenesis via suppressing the STAT3/Snail. Pathw. J. Cell. Biochem. 120, 10342–10350 (2019). (PMID: 10.1002/jcb.28318) S. Migliaccio, V.M. Bimonte, Z.M. Besharat, C. Sabato, A. Lenzi, C. Crescioli, E. Ferretti, Environmental contaminants acting as endocrine disruptors modulate atherogenic processes: new risk factors for cardiovascular diseases in women? Biomolecules 12, 44 (2021). (PMID: 35053192877356310.3390/biom12010044) A.G. Bakr, E.H. Hassanein, F.E. Ali, E.A. El-Shoura, Combined apocynin and carvedilol protect against cadmium-induced testicular damage via modulation of inflammatory response and redox-sensitive pathways. Life Sci. 311, 121152 (2022). (PMID: 3633612510.1016/j.lfs.2022.121152)
معلومات مُعتمدة:	PRIN 20205HZBP8 Ministero dell'Università e della Ricerca; PON ARS01 00693 Ministero dell'Istruzione, dell'Università e della Ricerca
فهرسة مساهمة:	Keywords: Androgen receptor; Breast cancer; Cadmium; Cytokines; Endocrine disruptors; Estrogen receptors
المشرفين على المادة:	00BH33GNGH (Cadmium) 0 (Endocrine Disruptors) 0 (Androgens) 0 (Receptors, Androgen) 0 (Receptors, Estrogen) 0 (Cytokines) 0 (Estrogens) 0 (Interleukin-6)
تواريخ الأحداث:	Date Created: 20231118 Date Completed: 20240301 Latest Revision: 20240315
رمز التحديث:	20240315
مُعرف محوري في PubMed:	PMC10902028
DOI:	10.1007/s12020-023-03594-2
PMID:	37979099
قاعدة البيانات:	MEDLINE

Find this article in full text from Springer Verlag.

Full Text Finder

الوصف
تدمد:	1559-0100
DOI:	10.1007/s12020-023-03594-2