Lung Cancer
Volume 55, Issue 1 , Pages 1-14 , January 2007

Cyclin D1 in non-small cell lung cancer: A key driver of malignant transformation

  • Oliver Gautschi

      Affiliations

    • University of California Davis Cancer Center, Sacramento, USA
    • Clinic of Medical Oncology, University Hospital Bern, Bern, Switzerland
    • Corresponding Author InformationCorresponding author at: University of California Davis Cancer Center, 4501 X Street, Suite 3016, Sacramento, CA 95817, USA. Tel.: +1 916 734 3734; fax: +1 916 734 7946.
  • ,
  • Daniel Ratschiller

      Affiliations

    • Clinic of Medical Oncology, University Hospital Bern, Bern, Switzerland
  • ,
  • Mathias Gugger

      Affiliations

    • Department of Pathology, University of Bern, Bern, Switzerland
  • ,
  • Daniel C. Betticher

      Affiliations

    • Clinic of Medical Oncology, Hospital of Fribourg, Fribourg, Switzerland
  • ,
  • Jim Heighway

      Affiliations

    • Cancer Communications and Consultancy Ltd., Northwich, Cheshire, UK

Received 14 July 2006 ,Revised 25 September 2006 ,Accepted 26 September 2006.

References 

  1. Culotti J, Hartwell LH. Genetic control of the cell division cycle in yeast. Seven genes controlling nuclear division. Exp Cell Res. 1971;67:389–401
  2. Nurse P, Bissett Y. Gene required in G1 for commitment to cell cycle and in G2 for control of mitosis in fission yeast. Nature. 1981;292:558–560
  3. Lee MG, Nurse P. Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2. Nature. 1987;327:31–35
  4. Evans T, Rosenthal ET, Youngblom J, et al. Cyclin: a protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division. Cell. 1983;33:389–396
  5. Sanchez I, Dynlacht BD. New insights into cyclins, CDKs, and cell cycle control. Semin Cell Dev Biol. 2005;16:311–321
  6. Sherr CJ, Roberts JM. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 1999;13:1501–1512
  7. Motokura T, Bloom T, Kim HG, et al. A novel cyclin encoded by a bcl1-linked candidate oncogene. Nature. 1991;350:512–515
  8. Matsushime H, Roussel MF, Ashmun RA, et al. Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle. Cell. 1991;65:701–713
  9. Xiong Y, Connolly T, Futcher B, et al. Human D-type cyclin. Cell. 1991;65:691–699
  10. Ewen ME. Relationship between Ras pathways and cell cycle control. Prog Cell Cycle Res. 2000;4:1–17
  11. Hinz M, Krappmann D, Eichten A, et al. NF-kappaB function in growth control: regulation of cyclin D1 expression and G0/G1-to-S-phase transition. Mol Cell Biol. 1999;19:2690–2698
  12. Rocha S, Martin AM, Meek DW, Perkins ND. p53 represses cyclin D1 transcription through downregulation of Bcl-3 and inducing increased association of the p52 NF-B subunit with histone deacetylase 1. Mol Cell Biol. 2003;23:4713–4727
  13. Kato JY, Matsuoka M, Strom DK, et al. Regulation of cyclin D-dependent kinase 4 (cdk4) by cdk4-activating kinase. Mol Cell Biol. 1994;14:2713–2721
  14. Kato J, Matsushime H, Hiebert SW, et al. Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4. Genes Dev. 1993;7:331–342
  15. Diehl JA, Cheng M, Roussel MF, et al. Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization. Genes Dev. 1998;12:3499–3511
  16. Guo Y, Yang K, Harwalkar J, et al. Phosphorylation of cyclin D1 at Thr 286 during S phase leads to its proteasomal degradation and allows efficient DNA synthesis. Oncogene. 2005;24:2599–2612
  17. Baldin V, Lukas J, Marcote MJ, et al. Cyclin D1 is a nuclear protein required for cell cycle progression in G1. Genes Dev. 1993;7:812–821
  18. Kranenburg O, van der Eb AJ, Zantema A. Cyclin D1 is an essential mediator of apoptotic neuronal cell death. EMBO J. 1996;15:46–54
  19. Sumrejkanchanakij P, Tamamori-Adachi M, Matsunaga Y, et al. Role of cyclin D1 cytoplasmic sequestration in the survival of postmitotic neurons. Oncogene. 2003;22:8723–8730
  20. Zwijsen RM, Buckle RS, Hijmans EM, et al. Ligand-independent recruitment of steroid receptor coactivators to estrogen receptor by cyclin D1. Genes Dev. 1998;12:3488–3498
  21. Knudsen KE, Arden KC, Cavenee WK. Multiple G1 regulatory elements control the androgen-dependent proliferation of prostatic carcinoma cells. J Biol Chem. 1998;273:20213–20222
  22. Qin C, Burghardt R, Smith R, et al. Peroxisome proliferator-activated receptor gamma agonists induce proteasome-dependent degradation of cyclin D1 and estrogen receptor alpha in MCF-7 breast cancer cells. Cancer Res. 2003;63:958–964
  23. Bienvenu F, Gascan H, Coqueret O. Cyclin D1 represses STAT3 activation through a Cdk4-independent mechanism. J Biol Chem. 2001;276:16840–16847
  24. Knudsen KE, Cavenee WK, Arden KC. D-type cyclins complex with the androgen receptor and inhibit its transcriptional transactivation ability. Cancer Res. 1999;59:2297–2301
  25. Bosch F, Jares P, Campo E, et al. PRAD-1/cyclin D1 gene overexpression in chronic lymphoproliferative disorders: a highly specific marker of mantle cell lymphoma. Blood. 1994;84:2726–2732
  26. Hoyer JD, Hanson CA, Fonseca R, et al. The (11;14) (q13;q32) translocation in multiple myeloma. A morphologic and immunohistochemical study. Am J Clin Pathol. 2000;113:831–837
  27. Schuuring E, Verhoeven E, Mooi WJ, et al. Identification and cloning of two overexpressed genes, U21B31/PRAD1 and EMS1, within the amplified chromosome 11q13 region in human carcinomas. Oncogene. 1992;7:355–361
  28. Faust JB, Meeker TC. Amplification and expression of the bcl-1 gene in human solid tumor cell lines. Cancer Res. 1992;52:2460–2463
  29. Jiang W, Kahn SM, Tomita N, et al. Amplification and expression of the human cyclin D gene in esophageal cancer. Cancer Res. 1992;52:2980–2983
  30. Buckley MF, Sweeney KJ, Hamilton JA, et al. Expression and amplification of cyclin genes in human breast cancer. Oncogene. 1993;8:2127–2133
  31. Gillett C, Fantl V, Smith R, et al. Amplification and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining. Cancer Res. 1994;54:1812–1817
  32. Hosokawa Y, Tu T, Tahara H, et al. Absence of cyclin D1/PRAD1 point mutations in human breast cancers and parathyroid adenomas and identification of a new cyclin D1 gene polymorphism. Cancer Lett. 1995;93:165–170
  33. Betticher DC, Heighway J, Hasleton PS, et al. Prognostic significance of CCND1 (cyclin D1) overexpression in primary resected non-small-cell lung cancer. Br J Cancer. 1996;73:294–300
  34. Quelle DE, Ashmun RA, Shurtleff SA, et al. Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts. Genes Dev. 1993;7:1559–1571
  35. 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
  36. Yu Q, Geng Y, Sicinski P. Specific protection against breast cancers by cyclin D1 ablation. Nature. 2001;411:1017–1021
  37. Alt JR, Cleveland JL, Hannink M, et al. Phosphorylation-dependent regulation of cyclin D1 nuclear export and cyclin D1-dependent cellular transformation. Genes Dev. 2000;14:3102–3114
  38. Gladden AB, Woolery R, Aggarwal P, et al. Expression of constitutively nuclear cyclin D1 in murine lymphocytes induces B-cell lymphoma. Oncogene. 2006;25:998–1007
  39. Gladden AB, Diehl JA. Location, location, location: the role of cyclin D1 nuclear localization in cancer. J Cell Biochem. 2005;96:906–913
  40. Franca-Koh J, Yeo M, Fraser E, et al. The regulation of glycogen synthase kinase-3 nuclear export by Frat/GBP. J Biol Chem. 2002;277:43844–43848
  41. Moreno-Bueno G, Rodriguez-Perales S, Sanchez-Estevez C, et al. Cyclin D1 gene (CCND1) mutations in endometrial cancer. Oncogene. 2003;22:6115–6118
  42. Benzeno S, Lu F, Guo M, et al. Identification of mutations that disrupt phosphorylation-dependent nuclear export of cyclin D1. Oncogene 2006 [Epub ahead of print].
  43. Lu F, Gladden AB, Diehl JA. An alternatively spliced cyclin D1 isoform, cyclin D1b, is a nuclear oncogene. Cancer Res. 2003;63:7056–7061
  44. 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;278:30339–30347
  45. Strohmaier H, Spruck CH, Kaiser P, et al. Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line. Nature. 2001;413:316–322
  46. Russell A, Thompson MA, Hendley J, Trute L, Armes J, Germain D. Cyclin D1 and D3 associate with the SCF complex and are coordinately elevated in breast cancer. Oncogene. 1999;18:1983–1991
  47. Betticher DC, Thatcher N, Altermatt HJ, et al. Alternate splicing produces a novel cyclin D1 transcript. Oncogene. 1995;11:1005–1011
  48. Lee C, Wang Q. Bioinformatics analysis of alternative splicing. Brief Bioinform. 2005;6:23–33
  49. Holley SL, Parkes G, Matthias C, et al. Cyclin D1 polymorphism and expression in patients with squamous cell carcinoma of the head and neck. Am J Pathol. 2001;159:1917–1924
  50. Howe D, Lynas C. The cyclin D1 alternative transcripts [a] and [b] are expressed in normal and malignant lymphocytes and their relative levels are influenced by the polymorphism at codon 241. Haematologica. 2001;86:563–569
  51. Holley SL, Heighway J, Hoban PR. Induced expression of human CCND1 alternative transcripts in mouse Cyl-1 knockout fibroblasts highlights functional differences. Int J Cancer. 2005;114:364–370
  52. Huang M, Spitz MR, Gu J, et al. Cyclin D1 gene polymorphism as a risk factor for oral premalignant lesions. Carcinogenesis 2006 [Epub ahead of print].
  53. Knudsen KE, Diehl JA, Haiman CA, et al. Cyclin D1: polymorphism, aberrant splicing and cancer risk. Oncogene. 2006;25:1620–1628
  54. Qiuling S, Yuxin Z, Suhua Z, et al. Cyclin D1 gene polymorphism and susceptibility to lung cancer in a Chinese population. Carcinogenesis. 2003;24:1499–1503
  55. Buch S, Zhu B, Davis AG, et al. Association of polymorphisms in the cyclin D1 and XPD genes and susceptibility to cancers of the upper aero-digestive tract. Mol Carcinog. 2005;42:222–228
  56. Spitz MR. Data presented at: new applications of molecular epidemiology in cancer. ASCO Educational Symposium. Atlanta, Georgia; 2006.
  57. Gautschi O, Hugli B, Ziegler A, et al. Cyclin D1 (CCND1) A870G gene polymorphism modulates smoking-induced lung cancer risk and response to platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients. Lung Cancer. 2006;51:303–311
  58. Baker SG, Kaprio J. Common susceptibility genes for cancer: search for the end of the rainbow. BMJ. 2006;332:1150–1152
  59. Marchetti A, Doglioni C, Barbareschi M, et al. Cyclin D1 and retinoblastoma susceptibility gene alterations in non-small cell lung cancer. Int J Cancer. 1998;75:187–192
  60. Mishina T, Dosaka-Akita H, Kinoshita I, et al. Cyclin D1 expression in non-small-cell lung cancers: its association with altered p53 expression, cell proliferation and clinical outcome. Br J Cancer. 1999;80:1289–1295
  61. Reissmann PT, Koga H, Figlin RA, et al., Lung Cancer Study Group  Amplification and overexpression of the cyclin D1 and epidermal growth factor receptor genes in non-small-cell lung cancer. J Cancer Res Clin Oncol. 1999;125:61–70
  62. Yang WI, Chung KY, Shin DH, et al. Cyclin D1 protein expression in lung cancer. Yonsei Med J. 1996;37:142–150
  63. Kwa HB, Michalides RJ, Dijkman JH, et al. The prognostic value of NCAM, p53 and cyclin D1 in resected non-small cell lung cancer. Lung Cancer. 1996;14:207–217
  64. Mate JL, Ariza A, Aracil C, et al. Cyclin D1 overexpression in non-small cell lung carcinoma: correlation with Ki67 labelling index and poor cytoplasmic differentiation. J Pathol. 1996;180:395–399
  65. Caputi M, De Luca L, Papaccio G, et al. Prognostic role of cyclin D1 in non small cell lung cancer: an immunohistochemical analysis. Eur J Histochem. 1997;41:133–138
  66. Nishio M, Koshikawa T, Yatabe Y, et al. Prognostic significance of cyclin D1 and retinoblastoma expression in combination with p53 abnormalities in primary, resected non-small cell lung cancers. Clin Cancer Res. 1997;3:1051–1058
  67. Lingfei K, Pingzhang Y, Zhengguo L, et al. A study on p16, pRb, cdk4 and cyclinD1 expression in non-small cell lung cancers. Cancer Lett. 1998;130:93–101
  68. Tanaka H, Fujii Y, Hirabayashi H, et al. Disruption of the RB pathway and cell-proliferative activity in non-small-cell lung cancers. Int J Cancer. 1998;79:111–115
  69. Brambilla E, Moro D, Gazzeri S, et al. Alterations of expression of Rb, p16(INK4A) and cyclin D1 in non-small cell lung carcinoma and their clinical significance. J Pathol. 1999;188:351–360
  70. Volm M, Koomagi R. Association of cyclin D1 expression in lung cancer and the smoking habits of patients. Cancer Lett. 1999;141:147–150
  71. Malusecka E, Zborek A, Krzyzowska-Gruca S. Changes in expression of pRb, p16 and cyclin D1 in non-small cell lung cancer: an immunohistochemical study. Folia Histochem Cytobiol. 1999;37:19–24
  72. Keum JS, Kong G, Yang SC, et al. Cyclin D1 overexpression is an indicator of poor prognosis in resectable non-small cell lung cancer. Br J Cancer. 1999;81:127–132
  73. Anton RC, Coffey DM, Gondo MM, et al. The expression of cyclins D1 and E in predicting short-term survival in squamous cell carcinoma of the lung. Mod Pathol. 2000;13:1167–1172
  74. Nguyen VN, Mirejovsky P, Mirejovsky T, et al. Expression of cyclin D1, Ki-67 and PCNA in non-small cell lung cancer: prognostic significance and comparison with p53 and bcl-2. Acta Histochem. 2000;102:323–338
  75. Gugger M, Kappeler A, Vonlanthen S, et al. Alterations of cell cycle regulators are less frequent in advanced non-small cell lung cancer than in resectable tumours. Lung Cancer. 2001;33:229–239
  76. Yamanouchi H, Furihata M, Fujita J, et al. Expression of cyclin E and cyclin D1 in non-small cell lung cancers. Lung Cancer. 2001;31:3–8
  77. Jin M, Inoue S, Umemura T, et al. Cyclin D1, p16 and retinoblastoma gene product expression as a predictor for prognosis in non-small cell lung cancer at stages I and II. Lung Cancer. 2001;34:207–218
  78. Ikehara M, Oshita F, Ito H, et al. Expression of cyclin D1 but not of cyclin E is an indicator of poor prognosis in small adenocarcinomas of the lung. Oncol Rep. 2003;10:137–139
  79. Esposito V, Baldi A, De Luca A, et al. Cell cycle related proteins as prognostic parameters in radically resected non-small cell lung cancer. J Clin Pathol. 2005;58:734–739
  80. Dworakowska D, Jassem E, Jassem J, et al. Prognostic value of cyclin D1 overexpression in correlation with pRb and p53 status in non-small cell lung cancer (NSCLC). J Cancer Res Clin Oncol. 2005;131:479–485
  81. Wang J, Miao LJ, Wu YM, et al. Expression of AKT2, cyclin D1, and MMP-9 and their correlations to clinicopathologic features of non-small cell lung cancer. Ai Zheng. 2006;25:69–72
  82. Betticher DC, Heighway J, Thatcher N, et al. Abnormal expression of CCND1 and RB1 in resection margin epithelia of lung cancer patients. Br J Cancer. 1997;75:1761–1768
  83. Kurasono Y, Ito T, Kameda Y, et al. Expression of cyclin D1, retinoblastoma gene protein, and p16 MTS1 protein in atypical adenomatous hyperplasia and adenocarcinoma of the lung. An immunohistochemical analysis. Virchows Arch. 1998;432:207–215
  84. Brambilla E, Gazzeri S, Moro D, et al. Alterations of Rb pathway (Rb-p16INK4-cyclin D1) in preinvasive bronchial lesions. Clin Cancer Res. 1999;5:243–250
  85. Lonardo F, Rusch V, Langenfeld J, et al. Overexpression of cyclins D1 and E is frequent in bronchial preneoplasia and precedes squamous cell carcinoma development. Cancer Res. 1999;59:2470–2476
  86. Ratschiller D, Heighway J, Gugger M, et al. Cyclin D1 overexpression in bronchial epithelia of patients with lung cancer is associated with smoking and predicts survival. J Clin Oncol. 2003;21:2085–2093
  87. Lantuejoul S, Soria JC, Morat L, et al. Telomere shortening and telomerase reverse transcriptase expression in preinvasive bronchial lesions. Clin Cancer Res. 2005;11:2074–2082
  88. Karlseder J, Zeillinger R, Schneeberger C, et al. Patterns of DNA amplification at band q13 of chromosome 11 in human breast cancer. Genes Chrom Cancer. 1994;9:42–48
  89. Vonlanthen S, Heighway J, Kappeler A, et al. p21 is associated with cyclin D1, p16INK4a and pRb expression in resectable non-small cell lung cancer. Int J Oncol. 2000;16:951–957
  90. Zhou P, Jiang W, Zhang YJ, et al. Antisense to cyclin D1 inhibits growth and reverses the transformed phenotype of human esophageal cancer cells. Oncogene. 1995;11:571–580
  91. Shapiro GI, Supko JG, Patterson A, et al. A phase II trial of the cyclin-dependent kinase inhibitor flavopiridol in patients with previously untreated stage IV non-small cell lung cancer. Clin Cancer Res. 2001;7:1590–1599
  92. Gries JM, Kasimis B, Schwarzenberger P, et al. Phase I study of HMR1275 (flavopiridol) in non-small cell lung cancer (NSCLC) patients after 24h IV administration in combination with paclitaxel and carboplatin. Proc Am Soc Clin Oncol. 2002;21:[abstr 372]
  93. Kasimis B, Rocha-Lima C, Cogswell J, et al. Phase I study evaluating 1-hour flavopiridol (HMR1275) in combination with docetaxel (D) in previously treated non-small cell lung cancer (NSCLC) patients (pts)(HMR1275B/1008). Proc Am Soc Clin Oncol. 2003;22:[abstr 2689]
  94. Fry DW, Harvey PJ, Keller PR, et al. Specific inhibition of cyclin-dependent kinase 4/6 by PD-0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther. 2004;3:1427–1438
  95. Faul MM, Engler TA, Sullivan KA, et al. Synthetic approaches to indolo[6,7-a]pyrrolo[3,4-c]carbazoles: potent cyclin D1/CDK4 inhibitors. J Org Chem. 2004;69:2967–2975

PII: S0169-5002(06)00530-7

doi: 10.1016/j.lungcan.2006.09.024

Lung Cancer
Volume 55, Issue 1 , Pages 1-14 , January 2007