Abstract
DNAs from 1,3-butadiene-induced mammary adenocarcinomas of B6C3F1 mice were examined for mutations in the Trp53 gene, the ras gene family and several components of the Wnt signaling pathway, including β-catenin (Catnb), Apc and Axin. Trp53 mutations were detected in 41% (7 out of 17) of tumors. Each tumor with a Trp53 mutation also exhibited loss of the wild-type Trp53 allele, supporting the importance of Trp53 inactivation during development of these tumors. Analyses of the Hras1, Kras2 and Nras proto-oncogenes revealed Hras1 mutations in 53% (9 out of 17) of tumors. Seven of these mutations were a G→C transversion in Hras1 codon 13, consistent with a 1,3-butadiene-specific Kras2 mutation previously reported in several other tumor types. Mutation screens in Catnb exon 2, the Apc mutation cluster region and the Catnb-binding domain of the Axin gene identified Catnb missense mutations in 3 out of 17 (18%) tumors. In total, mutations of the Trp53, Hras1 and/or Catnb genes were identified in 15 out of 17 1,3-butadiene-induced mammary adenocarcinomas. These results indicate that multiple genetic pathways are disrupted in chemically induced mammary tumors, and that studies in mouse models may help to understand the etiology of human breast cancers.
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References
Aberle H, Bauer A, Stappert J, Kispert A, Kemler R . 1997 EMBO J. 16: 3797–3804
Balmain A, Brown K . 1988 Adv. Cancer Res. 51: 147–182
Bos JL . 1989 Cancer Res. 49: 4682–4689
Dashwood RH, Suzui M, Nakagama H, Sugimura T, Nagao M . 1998 Cancer Res. 58: 1127–1129
de La Coste A, Romagnolo B, Billuart P, Renard CA, Buendia MA, Soubrane O, Fabre M, Chelly J, Beldjord C, Kahn A, Perret C . 1998 Proc. Natl. Acad. Sci. USA 95: 8847–8851
Devereux TR, Anna CH, Foley JF, White CM, Sills RC, Barrett JC . 1999 Oncogene 18: 4726–4733
Goodrow T, Reynolds S, Maronpot R, Anderson M . 1990 Cancer Res. 50: 4818–4823
Greenblatt MS, Bennett WP, Hollstein M, Harris CC . 1994 Cancer Res. 54: 4855–4878
Hart MJ, de los Santos R, Albert IN, Rubinfeld B, Polakis P . 1998 Curr. Biol. 8: 573–581
Hartmann A, Blaszyk H, Kovach JS, Sommer SS . 1997 Trends Genet. 13: 27–33
He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW . 1998 Science 281: 1509–1512
Henninghausen L . 2000 Oncogene 19: 966–967
Hong HH, Devereux TR, Melnick RL, Moomaw CR, Boorman GA, Sills RC . 2000 Toxicol. Pathol. 28: 529–534
IARC. 1992 IARC Monographs 54: 237–285
Koivisto P, Kilpelainen I, Rasanen I, Adler ID, Pacchierotti F, Peltonen K . 1999 Carcinogenesis 20: 1253–1259
Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, Vogelstein B, Clevers H . 1997 Science 275: 1784–1787
Leon J, Guerrero I, Pellicer A . 1987 Mol. Cell Biol. 7: 1535–1540
Lin SY, Xia W, Wang JC, Kwong KY, Spohn B, Wen Y, Pestell RG, Hung MC . 2000 Proc. Natl. Acad. Sci. USA 97: 4262–4266
Martin AM, Weber BL . 2000 J. Natl. Cancer Inst. 92: 1126–1135
Melnick RL, Huff J, Chou BJ, Miller RA . 1990 Cancer Res. 50: 6592–6599
Melnick RL, Sills RC . 2001 Chem. Biol. Interact. 135, 136: 27–42
Meng Q, Singh N, Heflich RH, Bauer MJ, Walker VE . 2000 Mutation Res. 464: 169–184
Miller JR, Hocking AM, Brown JD, Moon RT . 1999 Oncogene 18: 7860–7872
Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B, Kinzler KW . 1997 Science 275: 1787–1790
Morin PJ . 1999 Bioessays 21: 1021–1030
Moser AR, Mattes EM, Dove WF, Lindstrom MJ, Haag JD, Gould MN . 1993 Proc. Natl. Acad. Sci. USA 90: 8977–8981
National Toxicology Program. 2000 9th Report on Carcinogenesis US DHHS, Research Triangle Park, NC pp. III14–III17
Orford K, Orford CC, Byers SW . 1999 J. Cell Biol. 146: 855–868
Osborne RJ, Hamshere MG . 2000 Cancer Res. 60: 3706–3712
Polakis P . 1995 Curr. Opin. Genet. Dev. 5: 66–71
Rubinfeld B, Albert I, Porfiri E, Munemitsu S, Polakis P . 1997 Cancer Res. 57: 4624–4630
Russo IH, Russo J . 1996 Environ. Health Perspect. 104: 938–967
Satoh S, Daigo Y, Furukawa Y, Kato T, Miwa N, Nishiwaki T, Kawasoe T, Ishiguro H, Fujita M, Tokino T, Sasaki Y, Imaoka S, Murata M, Shimano T, Yamaoka Y, Nakamura Y . 2000 Nat. Genet. 24: 245–250
Sills RC, Hong HL, Boorman GA, Devereux TR, Melnick RL . 2001 Chem. Biol. Interact. 135, 136: 373–386
Tetsu O, McCormick F . 1999 Nature 398: 422–426
Thor A, Ohuchi N, Hand PH, Callahan R, Weeks MO, Theillet C, Lidereau R, Escot C, Page DL, Vilasi V, Schlom J . 1986 Lab. Invest. 55: 603–615
Tsukamoto AS, Grosschedl R, Guzman RC, Parslow T, Varmus HE . 1988 Cell 55: 619–625
Wiseman RW, Cochran C, Dietrich W, Lander ES, Soderkvist P . 1994 Proc. Natl. Acad. Sci. USA 91: 3759–3763
Zhuang S-M, Cochran C, Goodrow T, Wiseman RW, Soderkvist P . 1997 Cancer Res. 57: 2710–2714
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This study was supported by grants from the Swedish Cancer Society.
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Zhuang, SM., Wiseman, R. & Söderkvist, P. Frequent mutations of the Trp53, Hras1 and β-catenin (Catnb) genes in 1,3-butadiene-induced mammary adenocarcinomas in B6C3F1 mice. Oncogene 21, 5643–5648 (2002). https://doi.org/10.1038/sj.onc.1205649
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DOI: https://doi.org/10.1038/sj.onc.1205649