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Abnormal expression of MDM-2 in breast carcinomas

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Abstract

MDM-2 is a cellular oncoprotein that binds to the p53 protein and abrogates its growth-suppressing function. At least seven MDM-2 mRNAs and five proteins (p90, p85, p76, p74, and p57) have been reported in tissue culture. MDM-2 gene amplification occurs in human sarcomas and high-grade gliomas. MDM-2 overexpression without gene amplification has been reported in leukemias and lymphomas. Here we report MDM-2 mRNA overexpression in 24 (73%) out of 33 cases of human breast carcinoma as compared with normal breast tissue. The MDM-2 overexpression was seen in the absence of MDM-2 gene amplification. MDM-2 protein expression was studied by western blot analysis in 21 of these cases of carcinoma. We found complete concordance between MDM-2 mRNA overexpression and MDM-2 protein levels. MDM-2 proteins were overexpressed in 15 of 21 breast carcinoma tissue samples but not in normal breast tissue controls. Ten of these fifteen cases overexpressed MDM-2 p57 protein, two cases overexpressed both p57 and p90, and three cases overexpressed only p90. MDM-2 overexpression was confirmed by immunohistochemistry. p53 overexpression was also studied by immunohistochemistry; 69% of breast carcinomas that overexpressed the MDM-2 mRNA had detectable nuclear p53 protein. These findings demonstrate that MDM-2 oncoprotein expression is altered in primary human breast carcinomas at both mRNA and protein levels. In addition, our results suggest that MDM-2 p57 protein represents the main MDM-2 protein altered in breast carcinomas.

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Authors and Affiliations

  1. Hematopathology Program, Department of Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 72, 77030-4095, Houston, TX, USA

    Carlos E. Bueso-Ramos, Taghi Manshouri, Mohammad A. Haidar, Yun Yang, Patrick McCown, Armand Glassman & Maher Albitar

  2. Department of Pathology, The University of Texas M.D. Anderson Cancer Center, 77030, Houston, TX, USA

    Nelson Ordonez & Nour Sneige

Authors
  1. Carlos E. Bueso-Ramos
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  2. Taghi Manshouri
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  3. Mohammad A. Haidar
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  4. Yun Yang
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  5. Patrick McCown
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  6. Nelson Ordonez
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  7. Armand Glassman
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  8. Nour Sneige
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  9. Maher Albitar
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Bueso-Ramos, C.E., Manshouri, T., Haidar, M.A. et al. Abnormal expression of MDM-2 in breast carcinomas. Breast Cancer Res Tr 37, 179–188 (1996). https://doi.org/10.1007/BF01806499

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