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MAPKs’ status at early stages of renal carcinogenesis and tumors induced by ferric nitrilotriacetate

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Abstract

Renal cell carcinoma (RCC) is asymptomatic at early stages, and thus, initial diagnosis frequently occurs at advanced or even metastatic stages, leading to a high rate of mortality. Ferric nitrilotriacetate (FeNTA)-induced RCC model is a useful tool to analyze molecular events at different stages of the carcinogenesis process in vivo. MAPKs’ alterations seem to play an important role in the development and maintenance of human RCC tumors. Based on the above, p38α/β/γ, JNK1/2, and ERK1/2 statuses were studied at early stages of FeNTA-induced renal carcinogenesis (1 and 2 months of carcinogen treatment) as well as in tumor tissue. MAPKs showed distinct response along carcinogenesis process, either as total proteins and/or as their phosphorylated forms. While the increase in total and phospho-p38α/β levels became lower as carcinogenesis progressed, p38γ overexpression grew. Instead, total JNK2 diminished, but JNK1 was elevated at all studied times, and p-JNK1 levels increased at early stages, but not in tumors. In contrast, p-JNK2 rose at 2 months of treatment and in tumor tissue. Increased levels of p-ERK1/2 were observed at all stages analyzed. Very interestingly, at 1 and 2 months of FeNTA treatment, no alterations in MAPKs were found in liver or lung, where no primary tumors are induced with the scheme of FeNTA administration followed here. In conclusion, MAPKs’ behavior evolved differentially as renal carcinogenesis advanced, even among isoforms of the same family, but it did not change in other tissues. All this strongly suggests a role of these kinases in FeNTA-induced RCC tumor development and maintenance.

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References

  1. Vasudev NS, Selby PJ, Banks RE (2012) Renal cancer biomarkers: the promise of personalized care. BMC Med 27(10):112

    Article  Google Scholar 

  2. Okada S, Midorikawa O (1982) Induction of the rat renal adenocarcinoma by Fe-nitrilotriacetate (Fe-NTA). Jpn Arch Intern Med 29:485–491

    CAS  Google Scholar 

  3. Ebina Y, Okada S, Hamasaki S, Ogino F, Li JL, Midorikawa O (1986) Nephrotoxicity and renal cell carcinoma after use of iron and aluminum-nitrilotriacetate complexes in rats. J Natl Cancer Inst 76:107–113

    CAS  PubMed  Google Scholar 

  4. Li JL, Okada S, Hamazaki S, Ebina Y, Midorikawa O (1987) Subacute nephrotoxicity and induction of renal cell carcinoma in mice treated with ferric nitrilotriacetate. Cancer Res 47:1867–1869

    CAS  PubMed  Google Scholar 

  5. Athar M, Iqbal M (1998) Ferric nitrilotriacetate promotes N-diethylnitrosamine-induced renal tumorigenesis in the rat: implications for the involvement of oxidative stress. Carcinogenesis 19:1133–1139

    Article  CAS  PubMed  Google Scholar 

  6. Jahangir T, Sultana S (2006) Modulatory effects of Pluchea lanceolata against chemically induced oxidative damage, hyperproliferation and two-stage renal carcinogenesis in Wistar rats. Mol Cell Biochem 291:175–185

    Article  CAS  PubMed  Google Scholar 

  7. Vargas-Olvera CY, Sánchez-González DJ, Solano JD, Aguilar-Alonso FA, Montalvo-Muñoz F, Martínez-Martínez CM, Medina-Campos ON, Ibarra-Rubio ME (2012) Characterization of N-diethylnitrosamine-initiated and ferric nitrilotriacetate-promoted renal cell carcinoma experimental model and effect of a tamarind seed extract against acute nephrotoxicity and carcinogenesis. Mol Cell Biochem 369:105–117

    Article  CAS  PubMed  Google Scholar 

  8. Hiroyasu M, Ozeki M, Kohda H, Echizenya M, Tanaka T, Hiai H, Toyokuni S (2002) Specific allelic loss of p16 (INK4A) tumor suppressor gene after weeks of iron-mediated oxidative damage during rat renal carcinogenesis. Am J Pathol 160:419–424

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Taniai E, Hayashi H, Yafune A, Watanabe M, Akane H, Suzuki K, Mitsumori K, Shibutani M (2012) Cellular distribution of cell cycle-related molecules in the renal tubules of rats treated with renal carcinogens for 28 days: relationship between cell cycle aberration and carcinogenesis. Arch 86:1453–1464

    CAS  Google Scholar 

  10. Bahnemann R, Leibold E, Kittel B, Mellert W, Jäckh R (1998) Different patterns of kidney toxicity after subacute administration of Na-nitrilotriacetic acid and Fe-nitrilotriacetic acid to Wistar rats. Toxicol Sci 46:166–175

    Article  CAS  PubMed  Google Scholar 

  11. Umemura T, Sai K, Takagi A, Hasegawa R, Kurokawa Y (1990) Oxidative DNA damage, lipid peroxidation and nephrotoxicity induced in the rat kidney after ferric nitrilotriacetate administration. Cancer Lett 54:95–100

    Article  CAS  PubMed  Google Scholar 

  12. Toyokuni S, Uchida K, Okamoto K (1994) Formation of 4-hydroxy-2-nonenal-modified proteins in the renal proximal tubules of rats treated with a renal carcinogen, ferric nitrilotriacetate. Natl Acad Sci 91:2616–2620

    Article  CAS  Google Scholar 

  13. Chen L, Wang Y, Kairaitis LK, Wang Y, Zhang BH, Harris DC (2001) Molecular mechanisms by which iron induces nitric oxide synthesis in cultured proximal tubule cells. Exp Nephrol 9:198–204

    Article  CAS  PubMed  Google Scholar 

  14. Gago-Dominguez M, Castelao JE (2006) Lipid peroxidation and renal cell carcinoma: further supportive evidence and new mechanistic insights. Free Radic Biol Med 40:721–733

    Article  CAS  PubMed  Google Scholar 

  15. Bosetti C, Scotti L, Maso LD, Talamini R, Montella M, Negri E, Ramazzotti V, Franceschi S, La Vecchia C (2007) Micronutrients and the risk of renal cell cancer: a case-control study from Italy. Int J Cancer 120:892–896

    Article  CAS  PubMed  Google Scholar 

  16. Bosetti C, Rossi M, McLaughlin JK, Negri E, Talamini R, Lagiou P, Montella M, Ramazzotti V, Franceschi S, LaVecchia C (2007) Flavonoids and the risk of renal cell carcinoma. Cancer Epidemiol Biomark Prev 16:98–101

    Article  CAS  Google Scholar 

  17. Kim EK, Choi EJ (2010) Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta 1802:396–405

    Article  CAS  PubMed  Google Scholar 

  18. Peti W, Page R (2013) Molecular basis of MAP kinase regulation. Protein Sci 22:1698–1710

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Yang SH, Sharrocks AD, Whitmarsh AJ (2013) MAP kinase signalling cascades and transcriptional regulation. Gene 513:1–13

    Article  CAS  PubMed  Google Scholar 

  20. Cuadrado A, Nebreda AR (2010) Mechanisms and functions of p38 MAPK signalling. Biochem J 429:403–417

    Article  CAS  PubMed  Google Scholar 

  21. Han J, Sun P (2007) The pathways to tumor suppression via route p38. Trends Biochem Sci 32:364–371

    Article  CAS  PubMed  Google Scholar 

  22. Hui L, Bakiri L, Stepniak E, Wagner EF (2007) p38alpha: a suppressor of cell proliferation and tumorigenesis. Cell Cycle 6:2429–2433

    Article  CAS  PubMed  Google Scholar 

  23. Koul HK, Pal M, Koul S (2013) Role of p38 MAP kinase signal transduction in solid tumors. Genes Cancer 4:342–359

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Tang J, Qi X, Mercola D, Han J, Chen G (2005) Essential role of p38gamma in K-Ras transformation independent of phosphorylation. J Biol Chem 280:23910–23917

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Samaras V, Tsopanomichalou M, Stamatelli A, Arnaoutoglou C, Samaras E, Arnaoutoglou M, Poulias H, Barbatis C (2009) Is there any potential link among caspase-8, p-p38 MAPK and bcl-2 in clear cell renal cell carcinomas? A comparative immunohistochemical analysis with clinical connotations. Diagn Pathol 4:7

    Article  PubMed Central  PubMed  Google Scholar 

  26. Ozbek E, Aliskan T, Otunctemur A, Calik G, Cakir S, Dursun M, Somay A (2012) Comparison of tumor grade and stage with nuclear factor kappa b and p38 mitogene activated protein kinase expressions in renal cell cancer. Arch Ital Urol Androl 84:53–60

    PubMed  Google Scholar 

  27. Ambrose M, Ryan A, O’Sullivan GC, Dunne C, Barry OP (2006) Induction of apoptosis in renal cell carcinoma by reactive oxygen species: involvement of extracellular signal-regulated kinase 1/2, p38delta/gamma, cyclooxygenase-2 down-regulation, and translocation of apoptosis-inducing factor. Mol Pharmacol 69:1879–1890

    Article  CAS  PubMed  Google Scholar 

  28. Sabapathy K, Wagner EF (2004) JNK2: a negative regulator of cellular proliferation. Cell Cycle 3:1520–1523

    Article  CAS  PubMed  Google Scholar 

  29. Bubici C, Papa S (2014) JNK signalling in cancer: in need of new, smarter therapeutic targets. Br J Pharmacol 171:24–37

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Mizuno R, Oya M, Shiomi T, Marumo K, Okada Y, Murai M (2004) Inhibition of MKP-1 expression potentiates JNK related apoptosis in renal cancer cells. J Urol 172:723–727

    Article  CAS  PubMed  Google Scholar 

  31. Takano Y, Iwata H, Yano Y, Miyazawa M, Virgona N, Sato H, Ueno K, Yano T (2010) Up-regulation of connexin 32 gene by 5-aza-2′-deoxycytidine enhances vinblastine-induced cytotoxicity in human renal carcinoma cells via the activation of JNK signalling. Biochem Pharmacol 80:463–470

    Article  CAS  PubMed  Google Scholar 

  32. Xu M, Hong M, Xie H (2013) Histone deacetylase inhibitors induce human renal cell carcinoma cell apoptosis through p-JNK activation. Nan Fang Yi Ke Da Xue Xue Bao 33:1409–1415

    CAS  PubMed  Google Scholar 

  33. An J, Liu H, Magyar CE, Guo Y, Veena MS, Srivatsan ES, Huang J, Rettig MB (2013) Hyperactivated JNK is a therapeutic target in pVHL-deficient renal cell carcinoma. Cancer Res 73:1374–1385

    Article  CAS  PubMed  Google Scholar 

  34. Bogoyevitch MA, Court NW (2004) Counting on mitogen-activated protein kinases–ERKs 3, 4, 5, 6, 7 and 8. Cell Signal 16:1345–1354

    Article  CAS  PubMed  Google Scholar 

  35. Deschênes-Simard X, Kottakis F, Meloche S, Ferbeyre G (2014) ERKs in cancer: friends or foes? Cancer Res 74:412–419

    Article  PubMed  Google Scholar 

  36. Oka H, Chatani Y, Hoshino R, Ogawa O, Kakehi Y, Terachi T, Okada Y, Kawaichi M, Kohno M, Yoshida O (1995) Constitutive activation of mitogen-activated protein (MAP) kinases in human renal cell carcinoma. Cancer Res 55:4182–4187

    CAS  PubMed  Google Scholar 

  37. Lee HJ, Kim DI, Kang GH, Kwak C, Ku JH, Moon KC (2009) Phosphorylation of ERK1/2 and prognosis of clear cell renal cell carcinoma. Urology 73:394–399

    Article  PubMed  Google Scholar 

  38. Campbell L, Nuttall R, Griffiths D, Gumbleton M (2009) Activated extracellular signal-regulated kinase is an independent prognostic factor in clinically confined renal cell carcinoma. Cancer 115:3457–3467

    Article  CAS  PubMed  Google Scholar 

  39. Marin-Kuan M, Nestler S, Verguet C, Bezençon C, Piguet D, Delatour T, Mantle P, Cavin C, Schilter B (2007) MAPK-ERK activation in kidney of male rats chronically fed ochratoxin A at a dose causing a significant incidence of renal carcinoma. Toxicol Appl Pharmacol 224:174–181

    Article  CAS  PubMed  Google Scholar 

  40. Cohen JD, Gard JM, Nagle RB, Dietrich JD, Monks TJ, Lau SS (2011) ERK crosstalks with 4EBP1 to activate cyclin D1 translation during quinol-thioether-induced tuberous sclerosis renal cell carcinoma. Toxicol Sci 124:75–87

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Salinas-Sánchez AS, Giménez-Bachs JM, Serrano-Oviedo L, Nam Cha S, Sánchez-Prieto R (2012) Role of mitogen-activated protein kinase (MAPK) in the sporadic renal cell carcinoma. Actas Urol Esp 36:99–103

    Article  PubMed  Google Scholar 

  42. Nogueira M, Kim HL (2008) Molecular markers for predicting prognosis of renal cell carcinoma. Urol Oncol 26:113–124

    Article  CAS  PubMed  Google Scholar 

  43. Shuch B, Amin A, Armstrong AJ, Eble JN, Ficarra V, Lopez-Beltran A, Martignoni G, Rini BI, Kutikov A (2014) Understanding pathologic variants of renal cell carcinoma: distilling therapeutic opportunities from biologic complexity. Eur Urol. doi:10.1016/j.eururo.2014.04.029

    PubMed  Google Scholar 

  44. Omori S, Hida M, Ishikura K, Kuramochi S, Awazu M (2000) Expression of mitogen-activated protein kinase family in rat renal development. Kidney Int 58:27–37

    Article  CAS  PubMed  Google Scholar 

  45. Omori S, Fukuzawa R, Hida M, Awazu M (2002) Expression of mitogen-activated protein kinases in human renal dysplasia. Kidney Int 61:899–906

    Article  CAS  PubMed  Google Scholar 

  46. Liu YT, Shang D, Akatsuka S, Ohara H, Dutta KK, Mizushima K, Naito Y, Yoshikawa T, Izumiya M, Abe K, Nakagama H, Noguchi N, Toyokuni S (2007) Chronic oxidative stress causes amplification and overexpression of ptprz1 protein tyrosine phosphatase to activate beta-catenin pathway. Am J Pathol 171:1978–1988

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. Rehman MU, Tahir M, Khan AQ, Khan R, Lateef A, Oday-O-Hamiza Qamar W, Ali F, Sultana S (2013) Chrysin suppresses renal carcinogenesis via amelioration of hyperproliferation, oxidative stress and inflammation: plausible role of NF-κB. Toxicol Lett 216:146–158

    Article  CAS  PubMed  Google Scholar 

  48. Fitzsimmons BL, Zattoni M, Svensson CI, Steinauer J, Hua XY, Yaksh TL (2010) Role of spinal p38alpha and beta MAPK in inflammatory hyperalgesia and spinal COX-2 expression. NeuroReport 21:313–317

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. Kim MK, Maeng YI, Sung WJ, Oh HK, Park JB, Yoon GS, Cho CH, Park KK (2013) The differential expression of TGF-β1, ILK and wnt signaling inducing epithelial to mesenchymal transition in human renal fibrogenesis: an immunohistochemical study. Int J Clin Exp Pathol 6:1747–1758

    PubMed Central  PubMed  Google Scholar 

  50. Hou SW, Zhi HY, Pohl N, Loesch M, Qi XM, Li RS, Basir Z, Chen G (2010) PTPH1 dephosphorylates and cooperates with p38gamma MAPK to increase ras oncogenesis through PDZ-mediated interaction. Cancer Res 70:2901–2910

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Rosenthal DT, Iyer H, Escudero S, Bao L, Wu Z, Ventura AC, Kleer CG, Arruda EM, Garikipati K, Merajver SD (2011) p38γ promotes breast cancer cell motility and metastasis through regulation of RhoC GTPase, cytoskeletal architecture, and a novel leading edge behavior. Cancer Res 71:6338–6349

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Yang K, Liu Y, Liu Z, Liu J, Liu X, Chen X, Li C, Zeng Y (2013) p38γ overexpression in gliomas and its role in proliferation and apoptosis. Sci Rep 3:2089

    PubMed Central  PubMed  Google Scholar 

  53. Qi X, Pohl NM, Loesch M, Hou S, Li R, Qin JZ, Cuenda A, Chen G (2007) p38alpha antagonizes p38gamma activity through c-Jun-dependent ubiquitin-proteasome pathways in regulating Ras transformation and stress response. J Biol Chem 282:31398–313408

    Article  CAS  PubMed  Google Scholar 

  54. Loesch M, Zhi HY, Hou SW, Qi XM, Li RS, Basir Z, Iftner T, Cuenda A, Chen G (2010) p38gamma MAPK cooperates with c-Jun in trans-activating matrix metalloproteinase 9. J Biol Chem 285:15149–15158

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Hui L, Zatloukal K, Scheuch H, Stepniak E, Wagner EF (2008) Proliferation of human HCC cells and chemically induced mouse liver cancers requires JNK1-dependent p21 downregulation. J Clin Invest 118:3943–3953

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. Mitra S, Lee JS, Cantrell M, Van den Berg CL (2011) c-Jun N-terminal kinase 2 (JNK2) enhances cell migration through epidermal growth factor substrate 8 (EPS8). J Biol Chem 286:15287–15297

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  57. Ishizawa J, Yoshida S, Oya M, Mizuno R, Shinojima T, Marumo K, Murai M (2004) Inhibition of the ubiquitin-proteasome pathway activates stress kinases and induces apoptosis in renal cancer cells. Int J Oncol 25:697–702

    CAS  PubMed  Google Scholar 

  58. Ou YC, Yang CR, Cheng CL, Raung SL, Hung YY, Chen CJ (2007) Indomethacin induces apoptosis in 786-O renal cell carcinoma cells by activating mitogen-activated protein kinases and AKT. Eur J Pharmacol 563:49–60

    Article  CAS  PubMed  Google Scholar 

  59. Liang YY, Zheng LS, Wu YZ, Peng LX, Cao Y, Cao X, Xie P, Huang BJ, Qian CN (2014) RASSF6 promotes p21(Cip1/Waf1)-dependent cell cycle arrest and apoptosis through activation of the JNK/SAPK pathway in clear cell renal cell carcinoma. Cell Cycle 13:1440–1449

    Article  CAS  PubMed  Google Scholar 

  60. Yoon HS, Monks TJ, Everitt JI, Walker CL, Lau SS (2002) Cell proliferation is insufficient, but loss of tuberin is necessary, for chemically induced nephrocarcinogenicity. Am J Physiol Renal Physiol 283:F262–F270

    Article  CAS  PubMed  Google Scholar 

  61. Vaidya VS, Shankar K, Lock EA, Dixon D, Mehendale HM (2003) Molecular mechanisms of renal tissue repair in survival from acute renal tubule necrosis: role of ERK1/2 pathway. Toxicol Pathol 31:604–618

    Article  CAS  PubMed  Google Scholar 

  62. Aguirre Ghiso JA, Kovalski K, Ossowski L (1999) Tumor dormancy induced by downregulation of urokinase receptor in human carcinoma involves integrin and MAPK signaling. J Cell Biol 147:89–104

    Article  CAS  PubMed  Google Scholar 

  63. Aguirre-Ghiso JA, Liu D, Mignatti A, Kovalski K, Ossowski L (2001) Urokinase receptor and fibronectin regulate the ERK(MAPK) to p38(MAPK) activity ratios that determine carcinoma cell proliferation or dormancy in vivo. Mol Biol Cell 12:863–879

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  64. Aguirre-Ghiso JA, Estrada Y, Liu D, Ossowski L (2003) ERK(MAPK) activity as a determinant of tumor growth and dormancy; regulation by p38(SAPK). Cancer Res 63:1684–1695

    CAS  PubMed  Google Scholar 

  65. Aguirre-Ghiso JA, Ossowski L, Rosenbaum SK (2004) Green fluorescent protein tagging of extracellular signal-regulated kinase and p38 pathways reveals novel dynamics of pathway activation during primary and metastatic growth. Cancer Res 64:7336–7345

    Article  CAS  PubMed  Google Scholar 

  66. Omori S, Hida M, Fujita H, Takahashi H, Tanimura S, Kohno M, Awazu M (2006) Extracellular signal-regulated kinase inhibition slows disease progression in mice with polycystic kidney disease. J Am Soc Nephrol 17:1604–1614

    Article  CAS  PubMed  Google Scholar 

  67. Omori S, Kitagawa H, Koike J, Fujita H, Hida M, Pringle KC, Awazu M (2008) Activated extracellular signal-regulated kinase correlates with cyst formation and transforming growth factor-beta expression in fetal obstructive uropathy. Kidney Int 73:1031–1037

    Article  CAS  PubMed  Google Scholar 

  68. Puisieux A, Brabletz T, Caramel J (2014) Oncogenic roles of EMT-inducing transcription factors. Nat Cell Biol 16:488–494

    Article  CAS  PubMed  Google Scholar 

  69. Ansar S, Iqbal M, Athar M (1999) Nordihydroguaiaretic acid is a potent inhibitor of ferric-nitrilotriacetate-mediated hepatic and renal toxicity, and renal tumour promotion, in mice. Carcinogenesis 20:599–606

    Article  CAS  PubMed  Google Scholar 

  70. Court NW, dos Remedios CG, Cordell J, Bogoyevitch MA (2002) Cardiac expression and subcellular localization of the p38 mitogen-activated protein kinase member, stress-activated protein kinase-3 (SAPK3). J Mol Cell Cardiol 34:413–426

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by Universidad Nacional Autónoma de México through Dirección General de Asuntos del Personal Académico—Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica (UNAM-DGAPA-PAPIIT) under projects IN227010 and IN221313, and through Faculty of Chemistry under PAIP number 4194-10, as well as by Consejo Nacional de Ciencia y Tecnología (CONACYT) under project 81026, given to MEIR. FAAA, CYVO, and TOPP received a fellowship from CONACYT. The authors appreciate the collaboration of M.V.Z. Lucía Macías Rosales for her valuable assistance in animal care and treatment. The funding sponsors had no involvement in this study design, the data collection, analysis and interpretation, the manuscript writing, or the decision to submit the manuscript for publication.

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  1. Laboratorio F-120, Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, 04510, Mexico, DF, Mexico

    Francisco A. Aguilar-Alonso, José D. Solano, Chabetty Y. Vargas-Olvera, Ignacio Pacheco-Bernal, Telma O. Pariente-Pérez & María Elena Ibarra-Rubio

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  1. Francisco A. Aguilar-Alonso
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  2. José D. Solano
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Correspondence to María Elena Ibarra-Rubio.

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Aguilar-Alonso, F.A., Solano, J.D., Vargas-Olvera, C.Y. et al. MAPKs’ status at early stages of renal carcinogenesis and tumors induced by ferric nitrilotriacetate. Mol Cell Biochem 404, 161–170 (2015). https://doi.org/10.1007/s11010-015-2375-5

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