Cyclins D in Regulation and Dysregulation of the Cell Cycle in Multiple Myeloma
Authors:
L. Kubiczková 1,2; M. Dúcka 1; L. Sedlaříková 1; F. Kryukov 1; R. Hájek 1,2; S. Ševčíková 1,2
Authors‘ workplace:
Babákova myelomová skupina, Ústav patologické fyziologie, LF MU, Brno
1; Oddělení klinické hematologie, FN Brno
2
Published in:
Klin Onkol 2013; 26(5): 313-318
Category:
Review
Overview
Multiple myeloma is the second most common hematooncological disease characterized by clonal proliferation of plasma cells and monoclonal immunoglobulin production. It is a heterogenous disease; however, dysregulation of cyclins D seems to be an early unifying pathogenic event in multiple myeloma. In almost all patients, there is increased expression level of at least one of the cyclins D. Nevertheless, the mechanism of this increase is unknown in many cases. Next to well‑known roles of cyclins D in the cell cycle, they have many other functions contributing to tumor cell progression. Cyclins D are prognostic markers and are also used for subclassification of multiple myeloma. In this review, we focus on significance of cyclins D in multiple myeloma.
Key words: Submitted: Accepted:
multiple myeloma – cyclin D – pathogenesis – cell cycle regulation – TC groups
This study was supported by scientific program of the Czech Ministry of Education, Youth and Sports MSM0021622434, Grant of the Ministry of Health NT14575, NT12130 and NT13190 and internal grant of Faculty of Medicine, Masaryk Univerzity MUNI/11/InGA17/2012.
The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.
12. 5. 2013
6. 6. 2013
Sources
1. Adam Z, Pour L, Krejčí M et al. Mnohočetný myelom. In: Adam Z, Krejčí M, Vorlíček J (eds). Speciální onkologie. Praha: Galén 2010: 321– 329.
2. Hájek R, Adam Z, Ščudla V et al. Diagnostika a léčba mnohočetného myelomu. Trans Hematol Dnes 2012; 18 (Suppl 1): 1– 89.
3. Fonseca R, Barlogie B, Bataille R et al. Genetics and cytogenetics of multiple myeloma: a workshop report. Cancer Res 2004; 64(4): 1546– 1558.
4. Bergsagel PL, Kuehl WM. Chromosome translocations in multiple myeloma. Oncogene 2001; 20(40): 5611– 5622.
5. Fonseca R, Bailey RJ, Ahmann GJ et al. Genomic abnormalities in monoclonal gammopathy of undetermined significance. Blood 2002; 100(4): 1417– 1424.
6. Bergsagel PL, Chesi M, Nardini E et al. Promiscuous translocations into immunoglobulin heavy chain switch regions in multiple myeloma. Proc Natl Acad Sci U S A 1996; 93(24): 13931– 13936.
7. Fonseca R, Blood E, Rue M et al. Clinical and biologic implications of recurrent genomic aberrations in myeloma. Blood 2003; 101(11): 4569– 4575.
8. Chesi M, Bergsagel PL. Many multiple myelomas: making more of the molecular mayhem. Hematology Am Soc Hematol Educ Program 2011; 2011: 344– 353.
9. Sun W, Lee DK, Lee CC et al. Differential expression of D‑type G1 cyclins during mouse development and liver regeneration in vivo. Mol Reprod Dev 1996; 43(4): 414– 420.
10. Xiong Y, Menninger J, Beach D et al. Molecular cloning and chromosomal mapping of CCND genes encoding human D‑type cyclins. Genomics 1992; 13(3): 575– 584.
11. Musgrove EA, Caldon CE, Barraclough J et al. Cyclin Das a therapeutic target in cancer. Nat Rev Cancer 2011; 11(8): 558– 572.
12. Knudsen KE, Diehl JA, Haiman CA et al. Cyclin D1: polymorphism, aberrant splicing and cancer risk. Oncogene 2006; 25(11): 1620– 1628.
13. Lu F, Gladden AB, Diehl JA. An alternatively spliced cyclin D1 isoform, cyclin D1b, is a nuclear oncogene. Cancer Res 2003; 63(21): 7056– 7061.
14. Solomon DA, Wang Y, Fox SR et al. Cyclin D1 splice variants. Differential effects on localization, RB phosphorylation, and cellular transformation. J Biol Chem 2003; 278(32): 30339– 30347.
15. Ho A, Dowdy SF. Regulation of G(1) cell‑ cycle progression by oncogenes and tumor suppressor genes. Curr Opin Genet Dev 2002; 12(1): 47– 52.
16. Sherr CJ, McCormick F. The RB and p53 pathways in cancer. Cancer Cell 2002; 2(2): 103– 112.
17. Weinberg RA. pRb and control of the cell cycle clock. In: Weinberg RA (ed.). The biology of cancer. New York: Garland Science 2007: 255– 307.
18. Sherr CJ, Roberts JM. CDK inhibitors: positive and negative regulators of G1- phase progression. Genes Dev 1999; 13(12): 1501– 1512.
19. Martinsson HS, Starborg M, Erlandsson F et al. Single cell analysis of G1 check points‑ the relationship between the restriction point and phosphorylation of pRb. Exp Cell Res 2005; 305(2): 383– 391.
20. Cheng M, Olivier P, Diehl JA et al. The p21(Cip1) and p27(Kip1) CDK ‚inhibitors‘ are essential activators of cyclin D‑ dependent kinases in murine fibroblasts. EMBO J 1999; 18(6): 1571– 1583.
21. Harbour JW, Luo RX, Dei Santi A et al. Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1. Cell 1999; 98(6): 859– 869.
22. Lundberg AS, Weinberg RA. Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin‑cdk complexes. Mol Cell Biol 1998; 18(2): 753– 761.
23. Foster DA, Yellen P, Xu L et al. Regulation of G1 Cell Cycle Progression: Distinguishing the Restriction Point from a Nutrient‑ Sensing Cell Growth Checkpoint(s). Genes Cancer 2010; 1(11): 1124– 1131.
24. Fantl V, Stamp G, Andrews A et al. Mice lacking cyclin D1 are small and show defects in eye and mammary gland development. Genes Dev 1995; 9(19): 2364– 2372.
25. Ciemerych MA, Kenney AM, Sicinska E et al. Development of mice expressing a single D‑type cyclin. Genes Dev 2002; 16(24): 3277– 3289.
26. Kozar K, Ciemerych MA, Rebel VI et al. Mouse development and cell proliferation in the absence of D‑ cyclins. Cell 2004; 118(4): 477– 491.
27. Furukawa Y, Kikuchi J, Nakamura M et al. Lineage‑ specific regulation of cell cycle control gene expression during haematopoietic cell differentiation. Br J Haematol 2000; 110(3): 663– 673.
28. Dai MS, Mantel CR, Xia ZB et al. An expansion phase precedes terminal erythroid differentiation of hematopoietic progenitor cells from cord blood in vitro and is associated with up‑ regulation of cyclin E and cyclin‑dependent kinase 2. Blood 2000; 96(12): 3985– 3987.
29. Kato JY, Sherr CJ. Inhibition of granulocyte differentiation by G1 cyclins D2 and D3 but not D1. Proc Natl Acad Sci U S A 1993; 90(24): 11513– 11517.
30. Zimmet JM, Ladd D, Jackson CW et al. A role for cyclin D3 in the endomitotic cell cycle. Mol Cell Biol 1997; 17(12): 7248– 7259.
31. Sun S, Zimmet JM, Toselli P et al. Overexpression of cyclin D1 moderately increases ploidy in megakaryocytes. Haematologica 2001; 86(1): 17– 23.
32. Solvason N, Wu WW, Kabra N et al. Induction of cell cycle regulatory proteins in anti‑immunoglobulin‑stimulated mature B lymphocytes. J Exp Med 1996; 184(2): 407– 417.
33. Tanguay DA, Chiles TC. Regulation of the catalytic subunit (p34PSK‑ J3/ cdk4) for the major D‑type cyclin in mature B lymphocytes. J Immunol 1996; 156(2): 539– 548.
34. Solvason N, Wu WW, Parry D et al. Cyclin D2 is essential for BCR‑ mediated proliferation and CD5 B cell development. Int Immunol 2000; 12(5): 631– 638.
35. Lam EW, Glassford J, Banerji L et al. Cyclin D3 compensates for loss of cyclin D2 in mouse B‑lymphocytes activated via the antigen receptor and CD40. J Biol Chem 2000; 275(5): 3479– 3484.
36. Motokura T, Bloom T, Kim HG et al. A novel cyclin encoded by a bcl1‑linked candidate oncogene. Nature 1991; 350(6318): 512– 515.
37. Fu K, Weisenburger DD, Greiner TC et al. Cyclin D1- negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling. Blood 2005; 106(13): 4315– 4321.
38. Delmer A, Ajchenbaum‑ Cymbalista F, Tang R et al. Overexpression of cyclin D2 in chronic B‑ cell malignancies. Blood 1995; 85(10): 2870– 2876.
39. Bergsagel PL, Kuehl WM, Zhan F et al. Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma. Blood 2005; 106(1): 296– 303.
40. Fonseca R, Bergsagel PL, Drach J et al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia 2009; 23(12): 2210– 2221.
41. Bergsagel PL, Kuehl WM. Molecular pathogenesis and a consequent classification of multiple myeloma. J Clin Oncol 2005; 23(26): 6333– 6338.
42. Kuroda Y, Sakai A, Tsuyama N et al. Ectopic cyclin D1 overexpression increases chemosensitivity but not cell proliferation in multiple myeloma. Int J Oncol 2008; 33(6): 1201– 1213.
43. Roué G, Pichereau V, Lincet H et al. Cyclin D1 mediates resistance to apoptosis through upregulation of molecular chaperones and consequent redistribution of cell death regulators. Oncogene 2008; 27(36): 4909– 4920.
44. Liu M, Aneja R, Liu C et al. Inhibition of the mitotic kinesin Eg5 up‑ regulates Hsp70 through the phosphatidylinositol 3- kinase/ Akt pathway in multiple myeloma cells. J Biol Chem 2006; 281(26): 18090– 18097.
45. Jirawatnotai S, Hu Y, Michowski W et al. A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers. Nature 2011; 474(7350): 230– 234.
46. 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(15): 3487– 3495.
47. 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(9): 2124– 2130.
Labels
Paediatric clinical oncology Surgery Clinical oncologyArticle was published in
Clinical Oncology
2013 Issue 5
Most read in this issue
- Management of Infections in Palliative and Terminal Cancer Care
- Chylous Ascites as a Serious Complication of the Neuroendocrine Tumor of Ileum – Case Report
- Nephroblastoma – 30-Years Period of its Treatment in the University Hospital Motol, Prague
- Patient with Atypical Neurocytoma – Case Report