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Br J Cancer. 1995 May; 71(5): 981–985.
PMCID: PMC2033791

Amplification of the MDM2 gene in human breast cancer and its association with MDM2 and p53 protein status.


The present study reports on the frequency of MDM2 gene amplification and MDM2 protein expression in a series of 100 breast carcinomas and its association with accumulation of the p53 protein. Of the 100 cases, frozen samples for 82 cases were available for Southern blotting. Three of the 82 (4%) demonstrated MDM2 gene amplification of up to 6-fold. Immunohistochemical analysis of the formalin-fixed, paraffin-embedded tumours demonstrated that 7/97 (7%) had nuclear expression for MDM2 in 10-50% of the tumour cells (type 2 staining) and were denoted MDM2+. Two of the MDM2-amplified samples were MDM2+ with one of the two tumours also displaying type 2 p53 nuclear staining. Finally at the protein level, MDM2+ tumours were significantly associated with tumours having low levels of p53 staining (0-10% cells positive) (P = 0.03). We conclude that MDM2 gene amplification occurs at a lower frequency in breast cancer than in non-epithelial tumours. Alterations in MDM2 and p53 may represent alternative pathways in tumorigenesis, but they are not mutually exclusive in all cases.

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  • Barnes DM, Hanby AM, Gillett CE, Mohammed S, Hodgson S, Bobrow LG, Leigh IM, Purkis T, MacGeoch C, Spurr NK, et al. Abnormal expression of wild type p53 protein in normal cells of a cancer family patient. Lancet. 1992 Aug 1;340(8814):259–263. [PubMed]
  • Bueso-Ramos CE, Yang Y, deLeon E, McCown P, Stass SA, Albitar M. The human MDM-2 oncogene is overexpressed in leukemias. Blood. 1993 Nov 1;82(9):2617–2623. [PubMed]
  • Cahilly-Snyder L, Yang-Feng T, Francke U, George DL. Molecular analysis and chromosomal mapping of amplified genes isolated from a transformed mouse 3T3 cell line. Somat Cell Mol Genet. 1987 May;13(3):235–244. [PubMed]
  • Fakharzadeh SS, Trusko SP, George DL. Tumorigenic potential associated with enhanced expression of a gene that is amplified in a mouse tumor cell line. EMBO J. 1991 Jun;10(6):1565–1569. [PMC free article] [PubMed]
  • Fearon ER, Cho KR, Nigro JM, Kern SE, Simons JW, Ruppert JM, Hamilton SR, Preisinger AC, Thomas G, Kinzler KW, et al. Identification of a chromosome 18q gene that is altered in colorectal cancers. Science. 1990 Jan 5;247(4938):49–56. [PubMed]
  • Finlay CA. The mdm-2 oncogene can overcome wild-type p53 suppression of transformed cell growth. Mol Cell Biol. 1993 Jan;13(1):301–306. [PMC free article] [PubMed]
  • Kessis TD, Slebos RJ, Han SM, Shah K, Bosch XF, Muñoz N, Hedrick L, Cho KR. p53 gene mutations and MDM2 amplification are uncommon in primary carcinomas of the uterine cervix. Am J Pathol. 1993 Nov;143(5):1398–1405. [PMC free article] [PubMed]
  • Khatib ZA, Matsushime H, Valentine M, Shapiro DN, Sherr CJ, Look AT. Coamplification of the CDK4 gene with MDM2 and GLI in human sarcomas. Cancer Res. 1993 Nov 15;53(22):5535–5541. [PubMed]
  • Kovar H, Auinger A, Jug G, Aryee D, Zoubek A, Salzer-Kuntschik M, Gadner H. Narrow spectrum of infrequent p53 mutations and absence of MDM2 amplification in Ewing tumours. Oncogene. 1993 Oct;8(10):2683–2690. [PubMed]
  • Ladanyi M, Cha C, Lewis R, Jhanwar SC, Huvos AG, Healey JH. MDM2 gene amplification in metastatic osteosarcoma. Cancer Res. 1993 Jan 1;53(1):16–18. [PubMed]
  • Leach FS, Tokino T, Meltzer P, Burrell M, Oliner JD, Smith S, Hill DE, Sidransky D, Kinzler KW, Vogelstein B. p53 Mutation and MDM2 amplification in human soft tissue sarcomas. Cancer Res. 1993 May 15;53(10 Suppl):2231–2234. [PubMed]
  • Momand J, Zambetti GP, Olson DC, George D, Levine AJ. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell. 1992 Jun 26;69(7):1237–1245. [PubMed]
  • Oliner JD, Kinzler KW, Meltzer PS, George DL, Vogelstein B. Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature. 1992 Jul 2;358(6381):80–83. [PubMed]
  • Oliner JD, Pietenpol JA, Thiagalingam S, Gyuris J, Kinzler KW, Vogelstein B. Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature. 1993 Apr 29;362(6423):857–860. [PubMed]
  • 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. 1993 Sep;8(9):2353–2360. [PubMed]
  • Preudhomme C, Quesnel B, Vachee A, Lepelley P, Collyn-D'Hooghe M, Wattel E, Fenaux P. Absence of amplification of MDM2 gene, a regulator of p53 function, in myelodysplastic syndromes. Leukemia. 1993 Aug;7(8):1291–1293. [PubMed]
  • Prosser J, Elder PA, Condie A, MacFadyen I, Steel CM, Evans HJ. Mutations in p53 do not account for heritable breast cancer: a study in five affected families. Br J Cancer. 1991 Feb;63(2):181–184. [PMC free article] [PubMed]
  • Reifenberger G, Liu L, Ichimura K, Schmidt EE, Collins VP. Amplification and overexpression of the MDM2 gene in a subset of human malignant gliomas without p53 mutations. Cancer Res. 1993 Jun 15;53(12):2736–2739. [PubMed]
  • Rubio MP, von Deimling A, Yandell DW, Wiestler OD, Gusella JF, Louis DN. Accumulation of wild type p53 protein in human astrocytomas. Cancer Res. 1993 Aug 1;53(15):3465–3467. [PubMed]
  • Sheikh MS, Shao ZM, Hussain A, Fontana JA. The p53-binding protein MDM2 gene is differentially expressed in human breast carcinoma. Cancer Res. 1993 Jul 15;53(14):3226–3228. [PubMed]
  • Shi SR, Key ME, Kalra KL. Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem. 1991 Jun;39(6):741–748. [PubMed]
  • Singh S, Simon M, Meybohm I, Jantke I, Jonat W, Maass H, Goedde HW. Human breast cancer: frequent p53 allele loss and protein overexpression. Hum Genet. 1993 Feb;90(6):635–640. [PubMed]
  • Warren W, Eeles RA, Ponder BA, Easton DF, Averill D, Ponder MA, Anderson K, Evans AM, DeMars R, Love R, et al. No evidence for germline mutations in exons 5-9 of the p53 gene in 25 breast cancer families. Oncogene. 1992 May;7(5):1043–1046. [PubMed]
  • Yoshida T, Sakamoto H, Terada M. Amplified genes in cancer in upper digestive tract. Semin Cancer Biol. 1993 Feb;4(1):33–40. [PubMed]
  • Wu X, Bayle JH, Olson D, Levine AJ. The p53-mdm-2 autoregulatory feedback loop. Genes Dev. 1993 Jul;7(7A):1126–1132. [PubMed]

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