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. 1998 Feb;89(2):221-7.
doi: 10.1111/j.1349-7006.1998.tb00552.x.

Role of MDM2 overexpression in doxorubicin resistance of breast carcinoma

A Suzuki  1 , M Toi, Y Yamamoto, S Saji, M Muta, T Tominaga
Affiliations

Role of MDM2 overexpression in doxorubicin resistance of breast carcinoma

A Suzuki et al. Jpn J Cancer Res. 1998 Feb.

Abstract

Several oncoproteins or tumor suppressor gene products have been indicated to be of value as predictors of the de novo resistance to cytotoxic agents. In this study, we have investigated the role of MDM2 (murine double minutes) overexpression in doxorubicin resistance of breast cancer. Immunocytochemical analysis demonstrated that MDM2-positive tumors, even with p53-negative phenotype, were significantly more resistant to doxorubicin treatment compared to MDM2-negative tumors. An in vitro experimental model using stable mdm2-transfected MCF-7 cells carrying wild-type p53 confirmed that the cells become approximately 3-fold more resistant to doxorubicin as a result of MDM2 overexpression, and the wild-type p53 function, such as the induction of p21Waf1 following DNA damage, was significantly suppressed. MDM2 overexpression is suggested to be a novel marker for predicting lack of response to doxorubicin treatment in breast cancer patients.

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References

    1. ) Cahilly‐Snyder , L. , Yang‐Feng , T. , Francke , U. and George , D. L.Molecular analysis and chromosomal mapping of amplified genes isolated from a transformed mouse 3T3 cell line . Somat. Cell Mol. Genet. , 13 , 235 – 244 ( 1987. ). - PubMed
    1. ) Fakharzadeh , S. S. , Trusko , S. P. and George , D. L.Tumorigenic potential associated with enhanced expression of a gene that is amplified in a mouse tumor cell line . EMBO J. , 10 , 1565 – 1569 ( 1991. ). - PMC - PubMed
    1. ) Oliner , J. D. , Kinzler , K. W. , Meltzer , P. S. , George , D. L. and Vogelstein , B.Amplification of a gene encoding a p53‐associated protein in human sarcomas . Nature , 358 , 80 – 83 ( 1992. ). - PubMed
    1. ) Momand , J. , Ambetti , G. P. , Olson , D. C. , George , D. and Levine , A. J.The mdm‐2 oncogene product forms a complex with the p53 protein and inhibits p53‐mediated transactivation . Cell , 69 , 1237 – 1245 ( 1992. ). - PubMed
    1. ) Barak , Y. , Juven , T. , Haffner , R. and Oren , M.mdm2 expression is induced by wild type p53 activity . EMBO J. , 12 , 461 – 468 ( 1993. ). - PMC - PubMed

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