Abnormal expression of MDM-2 in breast carcinomas
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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.
Key wordsgene amplification MDM-2 proteins oncoprotein p53 RT/PCR
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- 3.Barak Y, Juven T, Haffner R, Oren M: MDM2 expression is induced by wild type p53 activity. EMBO J 2: 461–468, 1993Google Scholar
- 13.Bueso-Ramos CE, Manshouri T, Haidar MA, Huh YO, Keating MJ, Albitar M: Multiple patterns of MDM-2 deregulation in human leukemias: Implications in leukemogenesis and prognosis. Leuk Lymphoma (in press)Google Scholar
- 22.Sambrook T, Fritsh E, Maniatis T: Molecular Cloning. A Laboratory Manual. Cold Spring Harbor Laboratory, Plainview, New York, 1989Google Scholar
- 30.Koopmans LH: An Introduction to Contemporary Statistics. PWS, Boston, MA, 1981Google Scholar
- 31.Olson DC, Marechal V, Momand J, Chen J, Romocki C, Levine AJ: Identification and characterization of multiple mdm-2 proteins and mdm-2-p53 protein complexes. Oncogene 8: 2352–2360, 1993Google Scholar