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Cyclins and cdks in development and cancer: a perspective

Oncogene volume 24, pages 2909–2915 (2005)Cite this article

Abstract

A fundamental aspect of cancer is dysregulated cell cycle control. Unlike normal cells that only proliferate when compelled to do so by developmental or other mitogenic signals in response to tissue growth needs, the proliferation of cancer cells proceeds essentially unchecked. This does not mean that cancer cell cycles are necessarily different from those found in normal cycling cells, but rather implies that cancer cells proliferate because they are no longer subject to proliferation-inhibitory influences arising from the stroma or from gene expression pattern changes consequent to ‘terminal’ differentiation, nor do they necessarily require extrinsic growth factors to recruit them into or maintain their proliferative state. Finally, cancer cells have also often avoided normal controls linked to cell cycle progression that halt proliferation in the presence of damaged DNA or other physiological insults. The result of these alterations is the inappropriate proliferation commonly associated with cancerous tumor formation. This review will summarize the current understanding of dysregulation of the G0/G1-to-S-phase transition in cancer cells, with particular emphasis on recent in vivo studies that suggest a need to rethink existing models of cell cycle control in development and tumorigenesis.

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References

  • Alkarain A, Jordan R and Slingerland J . (2004). J. Mammary Gland Biol. Neoplasia, 9, 67–80.

  • An HX, Beckmann MW, Reifenberger G, Bender HG and Niederacher D . (1999). Am. J. Pathol., 154, 113–118.

  • Baker GL, Landis MW and Hinds PW . (2005). Cell Cycle, 4, [Epub ahead of print].

  • Bartek J, Bartkova J and Lukas J . (1996). Curr. Opin. Cell Biol., 8, 805–814.

  • Bartkova J, Lukas J, Muller H, Lutzhoft D, Strauss M and Bartek J . (1994). Int. J. Cancer, 57, 353–361.

  • Bartkova J, Lukas J, Strauss M and Bartek J . (1995). Oncogene, 10, 775–778.

  • Berthet C, Aleem E, Coppola V, Tessarollo L and Kaldis P . (2003). Curr. Biol., 13, 1775–1785.

  • Bharadwaj R and Yu H . (2004). Oncogene, 23, 2016–2027.

  • Bienvenu F, Gascan H and Coqueret O . (2001). J. Biol. Chem., 276, 16840–16847.

  • Borg A, Sandberg T, Nilsson K, Johannsson O, Klinker M, Masback A, Westerdahl J, Olsson H and Ingvar C . (2000). J. Natl. Cancer Inst., 92, 1260–1266.

  • Bruce JL, Hurford Jr RK, Classon M, Koh J and Dyson N . (2000). Mol. Cell, 6, 737–742.

  • Buckley MF, Sweeney KJ, Hamilton JA, Sini RL, Manning DL, Nicholson RI, deFazio A, Watts CK, Musgrove EA and Sutherland RL . (1993). Oncogene, 8, 2127–2133.

  • Buschges R, Weber RG, Actor B, Lichter P, Collins VP and Reifenberger G . (1999). Brain Pathol., 9, 435–442, discussion 432–433.

  • Cairns P, Mao L, Merlo A, Lee DJ, Schwab D, Eby Y, Tokino K, van der Riet P, Blaugrund JE and Sidransky D . (1994). Science, 265, 415–417.

  • Cheng M, Sexl V, Sherr CJ and Roussel MF . (1998). Proc. Natl. Acad. Sci. USA, 95, 1091–1096.

  • Cheung TH, Yu MM, Lo KW, Yim SF, Chung TK and Wong YF . (2001). Cancer Lett., 166, 199–206.

  • Dannenberg JH, Schuijff L, Dekker M, van der Valk M and te Riele H . (2004). Genes Dev., 18, 2952–2962.

  • Delmer A, Ajchenbaum-Cymbalista F, Tang R, Ramond S, Faussat AM, Marie JP and Zittoun R . (1995). Blood, 85, 2870–2876.

  • Dickson C, Fantl V, Gillett C, Brookes S, Bartek J, Smith R, Fisher C, Barnes D and Peters G . (1995). Cancer Lett., 90, 43–50.

  • Draviam VM, Xie S and Sorger PK . (2004). Curr. Opin. Genet. Dev., 14, 120–125.

  • Du J, Widlund HR, Horstmann MA, Ramaswamy S, Ross K, Huber WE, Nishimura EK, Golub TR and Fisher DE . (2004). Cancer Cell., 6, 565–576.

  • Fajas L, Egler V, Reiter R, Miard S, Lefebvre AM and Auwerx J . (2003). Oncogene, 22, 4186–4193.

  • Filipits M, Jaeger U, Pohl G, Stranzl T, Simonitsch I, Kaider A, Skrabs C and Pirker R . (2002). Clin. Cancer Res., 8, 729–733.

  • Fujii M, Ishiguro R, Yamashita T and Tashiro M . (2001). Cancer Lett., 172, 187–192.

  • Furstenthal L, Kaiser BK, Swanson C and Jackson PK . (2001). J. Cell Biol., 152, 1267–1278.

  • Geng Y, Whoriskey W, Park MY, Bronson RT, Medema RH, Li T, Weinberg RA and Sicinski P . (1999). Cell, 97, 767–777.

  • Geng Y, Yu Q, Sicinska E, Das M, Bronson RT and Sicinski P . (2001a). Proc. Natl. Acad. Sci. USA, 98, 194–199.

  • Geng Y, Yu Q, Sicinska E, Das M, Schneider JE, Bhattacharya S, Rideout WM, Bronson RT, Gardner H and Sicinski P . (2003). Cell, 114, 431–443.

  • Geng Y, Yu Q, Whoriskey W, Dick F, Tsai KY, Ford HL, Biswas DK, Pardee AB, Amati B, Jacks T, Richardson A, Dyson N and Sicinski P . (2001b). Proc. Natl. Acad. Sci. USA, 98, 13138–13143.

  • Gillett C, Fantl V, Smith R, Fisher C, Bartek J, Dickson C, Barnes D and Peters G . (1994). Cancer Res., 54, 1812–1817.

  • Gillett C, Smith P, Gregory W, Richards M, Millis R, Peters G and Barnes D . (1996). Int. J. Cancer, 69, 92–99.

  • Grana X, Garriga J and Mayol X . (1998). Oncogene, 17, 3365–3383.

  • Gudas JM, Payton M, Thukral S, Chen E, Bass M, Robinson MO and Coats S . (1999). Mol. Cell. Biol., 19, 612–622.

  • He J, Olson JJ and James CD . (1995). Cancer Res., 55, 4833–4836.

  • Hedberg Y, Roos G, Ljungberg B and Landberg G . (2002). Acta Oncol., 41, 175–181.

  • Herman JG, Merlo A, Mao L, Lapidus RG, Issa JP, Davidson NE, Sidransky D and Baylin SB . (1995). Cancer Res., 55, 4525–4530.

  • Herwig S and Strauss M . (1997). Eur. J. Biochem., 246, 581–601.

  • Hinchcliffe EH, Li C, Thompson EA, Maller JL and Sluder G . (1999). Science, 283, 851–854.

  • Hirai H and Sherr CJ . (1996). Mol. Cell. Biol., 16, 6457–6467.

  • Inoue K and Sherr CJ . (1998). Mol. Cell. Biol., 18, 1590–1600.

  • Ito Y, Takeda T, Wakasa K, Tsujimoto M and Matsuura N . (2001). Anticancer Res., 21, 1043–1048.

  • Khatib ZA, Matsushime H, Valentine M, Shapiro DN, Sherr CJ and Look AT . (1993). Cancer Res., 53, 5535–5541.

  • Knudsen KE, Cavenee WK and Arden KC . (1999). Cancer Res., 59, 2297–2301.

  • Kozar K, Ciemerych MA, Rebel VI, Shigematsu H, Zagozdzon A, Sicinska E, Geng Y, Yu Q, Bhattacharya S, Bronson RT, Akashi K and Sicinski P . (2004). Cell, 118, 477–491.

  • Lamb J, Ramaswamy S, Ford HL, Contreras B, Martinez RV, Kittrell FS, Zahnow CA, Patterson N, Golub TR and Ewen ME . (2003). Cell, 114, 323–334.

  • Lammie GA, Fantl V, Smith R, Schuuring E, Brookes S, Michalides R, Dickson C, Arnold A and Peters G . (1991). Oncogene, 6, 439–444.

  • Lauper N, Beck AR, Cariou S, Richman L, Hofmann K, Reith W, Slingerland JM and Amati B . (1998). Oncogene, 17, 2637–2643.

  • Lin HM, Zhao L and Cheng SY . (2002). J. Biol. Chem., 277, 28733–28741.

  • Ma T, Van Tine BA, Wei Y, Garrett MD, Nelson D, Adams PD, Wang J, Qin J, Chow LT and Harper JW . (2000). Genes Dev., 14, 2298–2313.

  • Malumbres M and Barbacid M . (2001). Nat. Rev. Cancer, 1, 222–231.

  • Malumbres M, Hunt SL, Sotillo R, Martin J, Odajima J, Martin A, Dubus P, Ortega S and Barbacid M . (2003). Adv. Exp. Med. Biol., 532, 1–11.

  • Malumbres M, Sotillo R, Santamaria D, Galan J, Cerezo A, Ortega S, Dubus P and Barbacid M . (2004). Cell, 118, 493–504.

  • Massague J . (2004). Nature, 432, 298–306.

  • Matsuura I, Denissova NG, Wang G, He D, Long J and Liu F . (2004). Nature, 430, 226–231.

  • McIntosh GG, Anderson JJ, Milton I, Steward M, Parr AH, Thomas MD, Henry JA, Angus B, Lennard TW and Horne CH . (1995). Oncogene, 11, 885–891.

  • Meraldi P, Honda R and Nigg EA . (2004). Curr. Opin. Genet. Dev., 14, 29–36.

  • Morgan DO . (1997). Annu. Rev. Cell Dev. Biol., 13, 261–291.

  • Motokura T and Arnold A . (1993). Curr. Opin. Genet. Dev., 3, 5–10.

  • Murray AW . (2004). Cell, 116, 221–234.

  • Neuman E, Ladha MH, Lin N, Upton TM, Miller SJ, DiRenzo J, Pestell RG, Hinds PW, Dowdy SF, Brown M and Ewen ME . (1997). Mol. Cell. Biol., 17, 5338–5347.

  • Nevins JR . (2001). Hum. Mol. Genet., 10, 699–703.

  • Nobori T, Miura K, Wu DJ, Lois A, Takabayashi K and Carson DA . (1994). Nature, 368, 753–756.

  • Ohtani N, Yamakoshi K, Takahashi A and Hara E . (2004). J. Med. Invest., 51, 146–153.

  • Okuda M, Horn HF, Tarapore P, Tokuyama Y, Smulian AG, Chan PK, Knudsen ES, Hofmann IA, Snyder JD, Bove KE and Fukasawa K . (2000). Cell, 103, 127–140.

  • Ortega S, Malumbres M and Barbacid M . (2002). Biochim. Biophys. Acta, 1602, 73–87.

  • Ortega S, Prieto I, Odajima J, Martin A, Dubus P, Sotillo R, Barbero JL, Malumbres M and Barbacid M . (2003). Nat. Genet., 35, 25–31.

  • Pagano M and Jackson PK . (2004). Cell, 118, 535–538.

  • Payton M, Scully S, Chung G and Coats S . (2002). Oncogene, 21, 8529–8534.

  • Polyak K, Kato JY, Solomon MJ, Sherr CJ, Massague J, Roberts JM and Koff A . (1994). Genes Dev., 8, 9–22.

  • Rajagopalan H and Lengauer C . (2004). Nature, 432, 338–341.

  • Ratineau C, Petry MW, Mutoh H and Leiter AB . (2002). J. Biol. Chem., 277, 8847–8853.

  • Reissmann PT, Koga H, Figlin RA, Holmes EC and Slamon DJ . (1999). J. Cancer Res. Clin. Oncol., 125, 61–70.

  • Ren S and Rollins BJ . (2004). Cell, 117, 239–251.

  • Reutens AT, Fu M, Wang C, Albanese C, McPhaul MJ, Sun Z, Balk SP, Janne OA, Palvimo JJ and Pestell RG . (2001). Mol. Endocrinol., 15, 797–811.

  • Reynisdottir I, Polyak K, Iavarone A and Massague J . (1995). Genes Dev., 9, 1831–1845.

  • Robanus-Maandag E, Dekker M, van der Valk M, Carrozza ML, Jeanny JC, Dannenberg JH, Berns A and te Riele H . (1998). Genes Dev., 12, 1599–1609.

  • Rodrigo JP, Garcia LA, Ramos S, Lazo PS and Suarez C . (2000). Clin. Cancer Res., 6, 3177–3182.

  • Schmidt EE, Ichimura K, Reifenberger G and Collins VP . (1994). Cancer Res., 54, 6321–6324.

  • Shaughnessy Jr J, Gabrea A, Qi Y, Brents L, Zhan F, Tian E, Sawyer J, Barlogie B, Bergsagel PL and Kuehl M . (2001). Blood, 98, 217–223.

  • Sherr CJ . (1996). Science, 274, 1672–1677.

  • Sherr CJ and Roberts JM . (2004). Genes Dev., 18, 2699–2711.

  • Simon R, Struckmann K, Schraml P, Wagner U, Forster T, Moch H, Fijan A, Bruderer J, Wilber K, Mihatsch MJ, Gasser T and Sauter G . (2002). Oncogene, 21, 2476–2483.

  • Sotillo R, Dubus P, Martin J, de la Cueva E, Ortega S, Malumbres M and Barbacid M . (2001). EMBO J., 20, 6637–6647.

  • Spruck III CH, Gonzalez-Zulueta M, Shibata A, Simoneau AR, Lin MF, Gonzales F, Tsai YC and Jones PA . (1994). Nature, 370, 183–184.

  • Tetsu O and McCormick F . (2003). Cancer Cell, 3, 233–245.

  • Thomas DM, Carty SA, Piscopo DM, Lee JS, Wang WF, Forrester WC and Hinds PW . (2001). Mol. Cell, 8, 303–316.

  • Thomas DM, Johnson SA, Sims NA, Trivett MK, Slavin JL, Rubin BP, Waring P, McArthur GA, Walkley CR, Holloway AJ, Diyagama D, Grim JE, Clurman BE, Bowtell DD, Lee JS, Gutierrez GM, Piscopo DM, Carty SA and Hinds PW . (2004). J. Cell Biol., 167, 925–934.

  • Thomas DM, Yang HS, Alexander K and Hinds PW . (2003). Cancer Biol. Ther., 2, 124–130.

  • Tong W and Pollard JW . (2001). Mol. Cell. Biol., 21, 1319–1328.

  • Vielba R, Bilbao J, Ispizua A, Zabalza I, Alfaro J, Rezola R, Moreno E, Elorriaga J, Alonso I, Baroja A and de la Hoz C . (2003). Laryngoscope, 113, 167–172.

  • Wang C, Pattabiraman N, Zhou JN, Fu M, Sakamaki T, Albanese C, Li Z, Wu K, Hulit J, Neumeister P, Novikoff PM, Brownlee M, Scherer PE, Jones JG, Whitney KD, Donehower LA, Harris EL, Rohan T, Johns DC and Pestell RG . (2003). Mol. Cell. Biol., 23, 6159–6173.

  • Wei G, Lonardo F, Ueda T, Kim T, Huvos AG, Healey JH and Ladanyi M . (1999). Int. J. Cancer, 80, 199–204.

  • Weinberg RA . (1995). Cell, 81, 323–330.

  • Weinstat-Saslow D, Merino MJ, Manrow RE, Lawrence JA, Bluth RF, Wittenbel KD, Simpson JF, Page DL and Steeg PS . (1995). Nat. Med., 1, 1257–1260.

  • Yu Q, Geng Y and Sicinski P . (2001). Nature, 411, 1017–1021.

  • Yu Q, Ciemerych MA and Sicinski P . (2005). Oncogene (submitted).

  • Zariwala M, Liu J and Xiong Y . (1998). Oncogene, 17, 2787–2798.

  • Zhao J, Dynlacht B, Imai T, Hori T and Harlow E . (1998). Genes Dev., 12, 456–461.

  • Zou X, Ray D, Aziyu A, Christov K, Boiko AD, Gudkov AV and Kiyokawa H . (2002). Genes Dev., 16, 2923–2934.

  • Zwicker J, Brusselbach S, Jooss KU, Sewing A, Behn M, Lucibello FC and Muller R . (1999). Oncogene, 18, 19–25.

  • Zwijsen RM, Wientjens E, Klompmaker R, van der Sman J, Bernards R and Michalides RJ . (1997). Cell, 88, 405–415.

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Acknowledgements

We thank the members of their laboratories for helpful comments. AD and PWH are supported by NIH Grants AG20208, CA096527 and DE015302 to PWH. PS was supported by NIH Grant CA085296.

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Authors and Affiliations

  1. Department of Radiation Oncology, Molecular Oncology Research Institute, Tufts-New England Medical Center, Boston, MA, 02111, USA

    Amit Deshpande & Philip W Hinds

  2. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, 02115, USA

    Peter Sicinski

  3. Department of Pathology, Harvard Medical School, Boston, MA, 02115, USA

    Peter Sicinski

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  1. Amit Deshpande
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Deshpande, A., Sicinski, P. & Hinds, P. Cyclins and cdks in development and cancer: a perspective. Oncogene 24, 2909–2915 (2005). https://doi.org/10.1038/sj.onc.1208618

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