Targeting Mdmx to treat breast cancers with wild-type p53

Cell Death and Disease

Volumn 6, Issue 7, 2015, Pages

  Haupt, S ^a   Buckley, D ^a   Pang, J M B ^a   Panimaya, J ^a   Paul, P J ^a   Gamell, C ^a   Takano, E A ^a   Ying Lee, Y ^a   Hiddingh, S ^a   Rogers, T M ^a   Teunisse, A F A S ^b   Herold, M J ^c,d   Marine, J C ^e   Fox, S B ^a,d   Jochemsen, A ^b   Haupt, Y ^a,d,f  

^a PETER MACCALLUM CANCER CENTRE   (Australia)

^b LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^c WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH   (Australia)

^d UNIVERSITY OF MELBOURNE   (Australia)

^e UNIVERSITY OF LEUVEN   (Belgium)

^f MONASH UNIVERSITY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

DOXYCYCLINE; PROTEIN MDM2; PROTEIN MDMX; PROTEIN P21; PROTEIN P53; MDM4 PROTEIN, HUMAN; NUCLEAR PROTEIN; ONCOPROTEIN; TP53 PROTEIN, HUMAN;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BREAST CANCER; BREAST EPITHELIUM CELL; CANCER INHIBITION; CELL AGING; CELL SURVIVAL; CONTROLLED STUDY; DOWN REGULATION; DRUG TARGETING; FEMALE; GENE MUTATION; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; IN VIVO STUDY; MCF 7 CELL LINE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; ANIMAL; APOPTOSIS; BIOSYNTHESIS; BREAST TUMOR; CELL PROLIFERATION; DRUG SCREENING; EPITHELIUM CELL; GENE EXPRESSION REGULATION; GENETICS; MCF-7 CELL LINE; METABOLISM; MUTATION; PATHOLOGY;

ANIMALS; APOPTOSIS; BREAST NEOPLASMS; CELL PROLIFERATION; EPITHELIAL CELLS; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MCF-7 CELLS; MICE; MUTATION; NUCLEAR PROTEINS; PROTO-ONCOGENE PROTEINS; TUMOR SUPPRESSOR PROTEIN P53; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84954326860     PISSN: None     EISSN: 20414889     Source Type: Journal    
DOI: 10.1038/cddis.2015.173     Document Type: Article

References (49)

1. Levine AJ, Oren M. The first 30 years of p53: growing ever more complex. Nat Rev Cancer 2009; 9: 749-758.
2. Zuckerman V, Wolyniec K, Sionov RV, Haupt S, Haupt Y. Tumor suppression by p53: the importance of apoptosis and cellular senescence. J Pathol 2009; 219: 3-15.
3. Selivanova G. Wild type p53 reactivation: from lab bench to clinic. FEBS Lett 2014; 588: 2628-2638.
4. Bieging KT, Mello SS, Attardi LD. Unravelling mechanisms of p53-mediated tumor suppression. Nat Rev Cancer 2014; 14: 359-370.
5. Soussi T, Wiman KG. Shaping genetic alterations in human cancer: the p53 mutation paradigm. Cancer Cell 2007; 12: 303-312.
6. Wade M, Li YC, Wahl GM. MDM2 MDMX and p53 in oncogenesis and cancer therapy. Nat Rev Cancer 2013; 13: 83-96.
7. Marine JC. MDM2 and MDMX in cancer and development. Curr Top Dev Biol 2011; 94: 45-75.
8. Haupt Y, Maya R, Kazaz A, Oren M. Mdm2 promotes the rapid degradation of p53. Nature 1997; 387: 296-299.
9. Kubbutat MH, Jones SN, Vousden KH. Regulation of p53 stability by Mdm2. Nature 1997; 387: 299-303.
10. Marine JC, Dyer MA, Jochemsen AG. MDMX: from bench to bedside. J Cell Sci 2007; 120: 371-378.
11. Ito M, Barys L, O'Reilly T, Young S, Gorbatcheva B., Monahan J et al. Comprehensive mapping of p53 pathway alterations reveals an apparent role for both SNP309 and MDM2 amplification in sarcomagenesis. Clin Cancer Res 2011; 17: 416-426.
12. Laurie NA, Donovan SL, Shih CS, Zhang J, Mills N., Fuller C et al. Inactivation of the p53 pathway in retinoblastoma. Nature 2006; 444: 61-66.
13. Gembarska A, Luciani F, Fedele C, Russell E.A., Dewaele M., Villar S et al. MDM4 is a key therapeutic target in cutaneous melanoma. Nat Med 2012; 18: 1239-1247.
14. Yu Q, Li Y, Mu K, Li Z., Meng Q, Wu X et al. Amplification of Mdmx and overexpression of MDM2 contribute to mammary carcinogenesis by substituting for p53 mutations. Diagn Pathol 2014; 9: 71.
15. Danovi D, Meulmeester E, Pasini D, Migliorini D., Capra M, Frenk R et al. Amplification of Mdmx (or Mdm4) directly contributes to tumor formation by inhibiting p53 tumor suppressor activity. Mol Cell Biol 2004; 24: 5835-5843.
16. Dumay A, Feugeas JP, Wittmer E, Lehmann-Che J, Bertheau P, Espie M et al. Distinct tumor protein p53 mutants in breast cancer subgroups. Int J Cancer 2013; 132: 1227-1231.
17. Bertheau P, Lehmann-Che J, Varna M, Dumay A., Poirot B, Porcher R et al. p53 in breast cancer subtypes and new insights into response to chemotherapy. Breast 2013; 22: S27-S29.
18. Walerych D, Napoli M, Collavin L, Del Sal G. The rebel angel: mutant p53 as the driving oncogene in breast cancer. Carcinogenesis 2012; 33: 2007-2017.
19. Cheang MC, Chia SK, Voduc D, Gao D, Leung S., Snider J et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst 2009; 101: 736-750.
20. Lam S, Lodder K, Teunisse AF, Rabelink M.J., Schutte M., Jochemsen AG. Role of Mdm4 in drug sensitivity of breast cancer cells. Oncogene 2010; 29: 2415-2426.
21. Munoz-Espin D., Serrano M. Cellular senescence: from physiology to pathology. Nat Rev Mol Cell Biol 2014; 15: 482-496.
22. Sherr CJ. Ink4-Arf locus in cancer and aging. Wiley Interdiscip Rev Dev Biol 2012; 1: 731-741.
23. Quesnel B, Preudhomme C, Fournier J, Fenaux P., Peyrat JP. MDM2 gene amplification in human breast cancer. Eur J Cancer 1994; 30A: 982-984.
24. Kulkarni DA, Vazquez A, Haffty BG, Bandera E.V., Hu W., Sun YY et al. A polymorphic variant in human MDM4 associates with accelerated age of onset of estrogen receptor negative breast cancer. Carcinogenesis 2009; 30: 1910-1915.
25. Marchetti A, Buttitta F, Girlando S, Dalla Palma P, Pellegrini S, Fina P et al. mdm2 gene alterations and mdm2 protein expression in breast carcinomas. J Pathol 1995; 175: 31-38.
26. Baunoch D, Watkins L, Tewari A, Reece M., Adams L, Stack R et al. MDM2 overexpression in benign and malignant lesions of the human breast. Int J Oncol 1996; 8: 895-899.
27. Graves B, Thompson T, Xia M, Janson C., Lukacs C, Deo D et al. Activation of the p53 pathway by small-molecule-induced MDM2 and MDMX dimerization. Proc Natl Acad Sci USA 2012; 109: 11788-11793.
28. Reincke S, Govbakh L, Wilhelm B, Jin H., Bogdanova N, Bremer M et al. Mutation analysis of the MDM4 gene in German breast cancer patients. BMC Cancer 2008; 8: 52.
29. Busuttil RA, Zapparoli GV, Haupt S, Fennell C, Wong S.Q., Pang JM et al. Role of p53 in the progression of gastric cancer. Oncotarget 2014; 5: 12016-12026.
30. Ponten F, Schwenk JM, Asplund A, Edqvist PH. The Human Protein Atlas as a proteomic resource for biomarker discovery. J Intern Med 2011; 270: 428-446.
31. Heminger K, Markey M, Mpagi M, Berberich SJ. Alterations in gene expression and sensitivity to genotoxic stress following HdmX or Hdm2 knockdown in human tumor cells harboring wild-type p53. Aging (Albany NY) 2009; 1: 89-108.
32. Wang H, Ma X, Ren S, Buolamwini J.K., Yan C. A small-molecule inhibitor of MDMX activates p53 and induces apoptosis. Mol Cancer Ther 2011; 10: 69-79.
33. Vaillant F, Merino D, Lee L, Breslin K., Pal B, Ritchie ME et al. Targeting BCL-2 with the BH3 mimetic ABT-199 in estrogen receptor-positive breast cancer. Cancer Cell 2013; 24: 120-129.
34. Brekman A, Singh KE, Polotskaia A, Kundu N, Bargonetti J. A p53-independent role of Mdm2 in estrogen-mediated activation of breast cancer cell proliferation. Breast Cancer Res 2011; 13: R3.
35. Martins CP, Brown-Swigart L, Evan GI. Modeling the therapeutic efficacy of p53 restoration in tumors. Cell 2006; 127: 1323-1334.
36. Ventura A, Kirsch DG, McLaughlin ME, Tuveson D.A., Grimm J., Lintault L et al. Restoration of p53 function leads to tumor regression in vivo. Nature 2007; 445: 661-665.
37. Xue W, Zender L, Miething C, Dickins R.A., Hernando E., Krizhanovsky V et al. Senescence and tumor clearance is triggered by p53 restoration in murine liver carcinomas. Nature 2007; 445: 656-660.
38. Khoo KH, Verma CS, Lane DP. Drugging the p53 pathway: understanding the route to clinical efficacy. Nat Rev Drug Discov 2014; 13: 217-236.
39. Ray-Coquard I., Blay JY, Italiano A, Le Cesne A, Penel N, Zhi J et al. Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study. Lancet Oncol 2012; 13: 1133-1140.
40. Marine JC. Pharmacological rescue of p53 in cancer therapy: widening the sensitive tumor spectrum by targeting MDMX. Cancer Cell 2010; 18: 399-400.
41. Garcia D, Warr MR, Martins CP, Brown Swigart L, Passegue E, Evan GI. Validation of MdmX as a therapeutic target for reactivating p53 in tumors. Genes Dev 2011; 25: 1746-1757.
42. Hu B, Gilkes DM, Farooqi B, Sebti SM, Chen J. MDMX overexpression prevents p53 activation by the MDM2 inhibitor Nutlin. J Biol Chem 2006; 281: 33030-33035.
43. Herold MJ, van den Brandt J, Seibler J, Reichardt HM. Inducible and reversible gene silencing by stable integration of an shRNA-encoding lentivirus in transgenic rats. Proc Natl Acad Sci USA 2008; 105: 18507-18512.
44. Louria-Hayon I., Grossman T, Sionov RV, Alsheich O, Pandolfi PP, Haupt Y. The promyelocytic leukemia protein protects p53 from Mdm2-mediated inhibition and degradation. J Biol Chem 2003; 278: 33134-33141.
45. Haupt S, di Agostino S, Mizrahi I, Alsheich-Bartok O, Voorhoeve M., Damalas A et al. Promyelocytic leukemia protein is required for gain of function by mutant p53. Cancer Res 2009; 69: 4818-4826.
46. Dimri G, Lee X, Basile G, Acosta M., Scott G, Roskelley C et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. PNAS 1995; 92: 9363-9367.
47. Giltnane JM, Rimm DL. Technology insight: Identification of biomarkers with tissue microarray technology. Nat Clin Pract Oncol 2004; 1: 104-111.
48. Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G., Hu Z et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 2004; 10: 5367-5374.
49. Takano EA, Rogers TM, Young RJ, Rayoo M, Kostos P., Ferguson R et al. The molecular characterisation of unusual subcutaneous spindle cell lesion of breast. J Clin Pathol 2012; 65: 746-750.