HDM4 is overexpressed in mantle cell lymphoma and its inhibition induces p21 expression and apoptosis

Modern Pathology

Volumn 23, Issue 3, 2010, Pages 381-391

  Liang, Mei ^a   Han, Xin ^a   Vadhan Raj, Saroj ^a   Nguyen, Martin ^a   Zhang, Yu H ^a   Fernandez, Michael ^a   Drakos, Elias ^a   Konoplev, Sergej N ^a   Yin, C Cameron ^a   Miranda, Roberto N ^a   McDonnell, Timothy J ^a   Medeiros, L Jeffrey ^a   Bueso Ramos, Carlos E ^a  

^a UNIVERSITY OF TEXAS   (United States)

Author keywords

HDM2; HDM4; HDMX; Mantle cell lymphoma; P21; P53

Indexed keywords

CASPASE 3; CELL CYCLE PROTEIN; CYCLIN D1; PROTEIN MDM2; PROTEIN MDMX; PROTEIN P21; PROTEIN P53; SMALL INTERFERING RNA;

ADULT; AGED; APOPTOSIS; ARTICLE; B LYMPHOCYTE; CANCER CELL CULTURE; CELL CYCLE PROGRESSION; CLINICAL ARTICLE; FEMALE; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; MALE; MANTLE CELL LYMPHOMA; NONHODGKIN LYMPHOMA; PRIORITY JOURNAL; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; TRANSCRIPTION INITIATION;

EID: 77649274289     PISSN: 08933952     EISSN: 15300285     Source Type: Journal    
DOI: 10.1038/modpathol.2009.170     Document Type: Article

References (37)

1. Toledo F, Wahl GM. Regulating the p53 pathway: in vitro hypotheses, in vivo veritas. Nat Rev Cancer 2006;6:909-923.
2. Shvarts A, Bazuine M, Dekker P, et al. Isolation and identification of the human homolog of a new p53-binding protein, Mdmx. Genomics 1997;43:34-42.
3. Shvarts A, Steegenga WT, Riteco N, et al. MDMX: a novel p53-binding protein with some functional properties of MDM2. EMBO J 1996;15:5349-5357.
4. Riemenschneider MJ, Buschges R, Wolter M, et al. Amplification and overexpression of the MDM4 (MDMX) gene from 1q32 in a subset of malignant gliomas without TP53 mutation or MDM2 amplification. Cancer Res 1999;59:6091-6096.
5. Danovi D, Meulmeester E, Pasini D, 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.
6. Bartel F, Schulz J, Bohnke A, et al. Significance of HDMX-S (or MDM4) mRNA splice variant overexpres-sion and HDMX gene amplification on primary soft tissue sarcoma prognosis. Int J Cancer 2005;117: 469-475.
7. Ramos YF, Stad R, Attema J, et al. Aberrant expression of HDMX proteins in tumor cells correlates with wild-type p53. Cancer Res 2001;61:1839-1842.
8. Stad R, Ramos YF, Little N, et al. Hdmx stabilizes Mdm2 and p53. J Biol Chem 2000;275:28039-28044.
9. Marine JC, Francoz S, Maetens M, et al. Keeping p53 in check: essential and synergistic functions of Mdm2 and Mdm4. Cell Death Differ 2006;13:927-934.
10. Marine JC, Jochemsen AG. Mdmx as an essential regulator of p53 activity. Biochem Biophys Res Commun 2005;331:750-760.
11. Stad R, Little NA, Xirodimas DP, et al. Mdmx stabilizes p53 and Mdm2 via two distinct mechanisms. EMBO Rep 2001;2:1029-1034.
12. Sharp DA, Kratowicz SA, Sank MJ, et al. Stabilization of the MDM2 oncoprotein by interaction with the structurally related MDMX protein. J Biol Chem 1999;274:38189-38196.
13. de Graaf P, Little NA, Ramos YF, et al. Hdmx protein stability is regulated by the ubiquitin ligase activity of Mdm2. J Biol Chem 2003;278:38315-38324.
14. Parant J, Chavez-Reyes A, Little NA, et al. Rescue of embryonic lethality in Mdm4-null mice by loss of Trp53 suggests a nonoverlapping pathway with MDM2 to regulate p53. Nat Genet 2001;29:92-95.
15. Linares LK, Hengstermann A, Ciechanover A, et al. HdmX stimulates Hdm2-mediated ubiquitination and degradation of p53. Proc Natl Acad Sci USA 2003;100:12009-12014.
16. Jin Y, Zeng SX, Sun XX, et al. MDMX promotes proteasomal turnover of p21 at G1 and early S phases independently of, but in cooperation with, MDM2. Mol Cell Biol 2008;28:1218-1229.
17. Bodrug SE, Warner BJ, Bath ML, et al. Cyclin D1 transgene impedes lymphocyte maturation and collaborates in lymphomagenesis with the myc gene. EMBO J 1994;13:2124-2130.
18. Lovec H, Grzeschiczek A, Kowalski MB, et al. Cyclin D1/bcl-1 cooperates with myc genes in the generation of B-cell lymphoma in transgenic mice. EMBO J 1994;13:3487-3495.
19. Onciu M, Schlette E, Medeiros LJ, et al. Cytogenetic findings in mantle cell lymphoma cases with a high level of peripheral blood involvement have a distinct pattern of abnormalities. Am J Clin Pathol 2001;116:886-892.
20. Fernandez V, Hartmann E, Ott G, et al. Pathogenesis of mantle-cell lymphoma: all oncogenic roads lead to dysregulation of cell cycle and DNA damage response pathways. J Clin Oncol 2005;23:6364-6369.
21. Greiner TC, Moynihan MJ, Chan WC, et al. p53 mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis. Blood 1996;87:4302-4310.
22. Louie DC, Offit K, Jaslow R, et al. p53 overexpression as a marker of poor prognosis in mantle cell lymphomas with t(11;14)(q13;q32). Blood 1995;86: 2892-2899.
23. Kienle D, Katzenberger T, Ott G, et al. Quantitative gene expression deregulation in mantle-cell lympho-ma: correlation with clinical and biologic factors. J Clin Oncol 2007;25:2770-2777.
24. Han X, Garcia-Manero G, McDonnell TJ, et al. HDM4 (HDMX) is widely expressed in adult pre-B acute lymphoblastic leukemia and is a potential therapeutic target. Mod Pathol 2007;20:54-62.
25. Amin HM, McDonnell TJ, Medeiros LJ, et al. Characterization of 4 mantle cell lymphoma cell lines. Arch Pathol Lab Med 2003;127:424-431.
26. Medeiros LJ, Estrov Z, Rassidakis GZ. Z-138 cell line was derived from a patient with blastoid variant mantle cell lymphoma. Leuk Res 2006;30:497-501.
27. Bueso-Ramos CE, Rocha FC, Shishodia S, et al. Expression of constitutively active nuclear-kappa B RelA transcription factor in blasts of acute myeloid leukemia. Hum Pathol 2004;35:246-253.
28. Shen Y, Iqbal J, Xiao L, et al. Distinct gene expression profiles in different B-cell compartments in human peripheral lymphoid organs. BMC Immunol 2004;5:20.
29. Giglio S, Mancini F, Gentiletti F, et al. Identification of an aberrantly spliced form of HDMX in human tumors: a new mechanism for HDM2 stabilization. Cancer Res 2005;65:9687-9694.
30. Rallapalli R, Strachan G, Cho B, et al. A novel MDMX transcript expressed in a variety of transformed cell lines encodes a truncated protein with potent p53 repressive activity. J Biol Chem 1999;274:8299-8308.
31. Mestre-Escorihuela C, Rubio-Moscardo F, Richter JA, et al. Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas. Blood 2007;109:271-280.
32. Lai R, McDonnell TJ, O'Connor SL, et al. Establishment and characterization of a new mantle cell lymphoma cell line, Mino. Leuk Res 2002;26: 849-855.
33. Daibata M, Kubonishi I, Eguchi T, et al. The establishment of Epstein-Barr virus nuclear antigen-positive (SP-50B) and Epstein-Barr virus nuclear antigen-negative (SP-53) cell lines with t(11;14)(q13;q32) chromosome abnormality from an intermediate lym-phocytic lymphoma. Cancer 1989;64:1248-1253.
34. Cho Y, Gorina S, Jeffrey PD, et al. Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations. Science 1994;265:346-355.
35. Young KH, Leroy K, Moller MB, et al. Structural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma: an international collaborative study. Blood 2008;112:3088-3098.
36. Coll-Mulet L, Iglesias-Serret D, Santidrian AF, et al. MDM2 antagonists activate p53 and synergize with genotoxic drugs in B-cell chronic lymphocytic leukemia cells. Blood 2006;107:4109-4114.
37. Drakos E, Atsaves V, Li J, et al. Stabilization and activation of p53 downregulates mTOR signaling through AMPK in mantle cell lymphoma. Leukemia 2009;23:784-790.