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Thirteen new p53 gene mutants identified among 41 human breast cancer cell lines

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The p53 tumor suppressor gene is frequently mutated in breast cancer. Here, we used direct sequencing to screen the complete coding sequence of the p53 gene from 41 human breast cancer cell lines. We identified 32 cell lines (78%) with a p53 gene alteration that predicted a change in the encoded protein. Thirty-one of these mutations were accompanied by loss of the other p53 allele. All mutations but one were unique and 27 mutations had previously been identified in uncultured human cancers. Ten mutations were predicted to encode a truncated p53 protein and 22 missense mutations were identified. p53 transcript expression was analyzed by semi-quantitative RT–PCR and p53 protein expression was determined by Western blotting. Our analyses revealed three p53 expression patterns: wild-type p53 cell lines had normal transcript levels and low or no detectable protein expression; cell lines with a p53 truncating mutation had low transcript levels and low or no detectable protein expression; and cell lines with a p53 missense mutation had highly variable transcript and protein expression levels. As a whole, our data represent a p53 mutation profile in breast cancer cell lines, providing a model for structural, functional and pharmacological studies on p53 in human cancer.

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  1. Vogelstein B, Lane D, Levine AJ: Surfing the p53 network Nature 408(6810): 307–310, 2000

    Article  PubMed  CAS  Google Scholar 

  2. Borresen-Dale AL: TP53 and breast cancer Hum Mutat 21(3): 292–300, 2003

    Article  PubMed  CAS  Google Scholar 

  3. Runnebaum IB, Nagarajan M, Bowman M, Soto D, Sukumar S: Mutations in p53 as potential molecular markers for human breast cancer Proc Natl Acad Sci USA 88(23): 10657–10661, 1991

    Article  PubMed  CAS  Google Scholar 

  4. Concin N, Zeillinger C, Tong D, Stimpfl M, Konig M, Printz D, Stonek F, Schneeberger C, Hefler L, Kainz C, et al: Comparison of p53 mutational status with mRNA and protein expression in a panel of 24 human breast carcinoma cell lines Breast Cancer Res Treat 79(1): 37–46, 2003

    Article  PubMed  CAS  Google Scholar 

  5. Ruiz-Ruiz MC, Lopez-Rivas A: p53-mediated up-regulation of CD95 is not involved in genotoxic drug-induced apoptosis of human breast tumor cells Cell Death Differ 6(3): 271–280, 1999

    Article  PubMed  CAS  Google Scholar 

  6. van de Wetering M, Barker N, Harkes IC, van der Heyden M, Dijk NJ, Hollestelle A, Klijn JG, Clevers H, Schutte M: Mutant E-cadherin breast cancer cells do not display constitutive Wnt signaling Cancer Res 61(1): 278–284, 2001

    PubMed  Google Scholar 

  7. Harkes IC, Elstrodt F, Dinjens WN, Molier M, Klijn JG, Berns EM, Schutte M: Allelotype of 28 human breast cancer cell lines and xenografts Br J Cancer 89(12): 2289–2292, 2003

    Article  PubMed  CAS  Google Scholar 

  8. Carbone D, Chiba I, Mitsudomi T: Polymorphism at codon 213 within the p53 gene Oncogene 6(9): 1691–1692, 1991

    PubMed  CAS  Google Scholar 

  9. Beckman G, Birgander R, Sjalander A, Saha N, Holmberg PA, Kivela A, Beckman L: Is p53 polymorphism maintained by natural selection? Hum Hered 44(5): 266–270, 1994

    Article  PubMed  CAS  Google Scholar 

  10. Teng DH, Perry WL 3rd, Hogan JK, Baumgard M, Bell R, Berry S, Davis T, Frank D, Frye C, Hattier T, et al: Human mitogen-activated protein kinase kinase 4 as a candidate tumor suppressor Cancer Res 57(19): 4177–4182, 1997

    PubMed  CAS  Google Scholar 

  11. Su GH, Hilgers W, Shekher MC, Tang DJ, Yeo CJ, Hruban RH, Kern SE: Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a genetically targeted tumor suppressor gene Cancer Res 58(11): 2339–2342, 1998

    PubMed  CAS  Google Scholar 

  12. Su GH, Song JJ, Repasky EA, Schutte M, Kern SE: Mutation rate of MAP2K4/MKK4 in breast carcinoma Hum Mutat 19(1): 81-84, 2002

    Article  PubMed  Google Scholar 

  13. Prives C, Hall PA: The p53 pathway J Pathol 187(1): 112–126, 1999

    Article  PubMed  CAS  Google Scholar 

  14. Momand J, Zambetti GP: Mdm-2: “big brother” of p53 J Cell Biochem 64(3): 343–352, 1997

    Article  PubMed  CAS  Google Scholar 

  15. Culbertson MR.: RNA surveillance. Unforeseen consequences for gene expression, inherited genetic disorders and cancerTrends Genet 15(2): 74–80, 1999

    Article  PubMed  CAS  Google Scholar 

  16. Berns EM, Foekens JA, Vossen R, Look MP, Devilee P, Henzen-Logmans SC, van Staveren IL, van Putten WL, Inganas M, Meijer-van Gelder ME, et al: Complete sequencing of TP53 predicts poor response to systemic therapy of advanced breast cancer Cancer Res 60(8): 2155–2162, 2000

    PubMed  CAS  Google Scholar 

  17. Norberg T, Lennerstrand J, Inganas M, Bergh J: Comparison between p53 protein measurements using the luminometric immunoassay and immunohistochemistry with detection of p53 gene mutations using cDNA sequencing in human breast tumors Int J Cancer 79(4): 376–383, 1998

    Article  PubMed  CAS  Google Scholar 

  18. Cho Y, Gorina S, Jeffrey PD, Pavletich NP: Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations Science 265(5170): 346–355, 1994

    Article  PubMed  CAS  Google Scholar 

  19. Rainwater R, Parks D, Anderson ME, Tegtmeyer P, Mann K: Role of cysteine residues in regulation of p53 function Mol Cell Biol 15(7): 3892–3903, 1995

    PubMed  CAS  Google Scholar 

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Funding was provided by Erasmus MC Revolving Fund and by the Dutch Cancer Society.

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Correspondence to Mieke Schutte.

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Wasielewski, M., Elstrodt, F., Klijn, J.G. et al. Thirteen new p53 gene mutants identified among 41 human breast cancer cell lines. Breast Cancer Res Treat 99, 97–101 (2006).

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