Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

RB and cyclin dependent kinase pathways: defining a distinction between RB and p16 loss in lung cancer

Oncogene volume 21, pages 6908–6914 (2002)Cite this article

Abstract

The genetic components of the RB:CDK:cyclin:p16 tumor suppressor pathway undergo mutational and epigenetic alterations in a wide range of human cancers and serve as critical targets for inactivation by the transforming oncoproteins of several DNA tumor viruses. Lung cancer has been a useful model system for these studies as it was the first tumor to demonstrate an important role for RB in the genesis of a common adult malignancy and was also the first human cancer to demonstrate genetic evidence for a multi-component RB:p16 tumor suppressor pathway. Lung tumorigenesis, however, is a complex disease process that requires longstanding carcinogen exposure in order to acquire somatic alterations at many distinct genetic loci. Understanding the multifunctional properties of RB to regulate cell proliferation, differentiation, and apoptosis and how they relate to the sequential accumulation of other clonal gene defects will be essential in order to understand the specific patterns of gene inactivation observed in different subtypes of lung cancer and to fulfill the promise of ‘molecular target’ therapeutics.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  • Abramson DH, Melson MR, Dunkel IJ, Frank CM . 2001 Ophthalmology 108: 1868–1876

  • Adams PD . 2001 Biochim. Biophys. Acta. 1471: M123–M133

  • Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M . 1988 Cell 53: 549–554

  • Bartek J, Lukas J . 2001 FEBS Lett. 490: 117–122

  • Bockhorn M, Frilling A, Kalinin V, Schroder S, Broelsch CE . 2000 Exp. Clin. Endocrinol. Diabetes 108: 49–53

  • Cagle PT, el-Naggar AK, Xu HJ, Hu SX, Benedict WF . 1997 Am. J. Pathol. 150: 393–400

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

  • Capella G, Matias-Guiu X, Ampudia X, de Leiva A, Perucho M, Prat J . 1996 Diagn. Mol. Pathol. 5: 45–52

  • Chen PL, Scully P, Shew JY, Wang JY, Lee WH . 1989 Cell 58: 1193–1198

  • Cheng M, Olivier P, Diehl JA, Fero M, Roussel MF, Roberts JM, Sherr CJ . 1999 EMBO J. 18: 1571–1583

  • Classon M, Salama S, Gorka C, Mulloy R, Braun P, Harlow E . 2000 Proc. Natl. Acad. Sci. USA 97: 10820–10825

  • Claudio PP, Howard CM, Pacilio C, Cinti C, Romano G, Minimo C, Maraldi NM, Minna JD, Gelbert L, Leoncini L, Tosi GM, Hicheli P, Caputi M, Giordano GG, Giordano A . 2000 Cancer Res. 60: 372–382

  • Cooper JA, Whyte P . 1989 Cell 58: 1009–1011

  • Coxon AB, Ward JM, Geradts J, Otterson GA, Zajac-Kaye M, Kaye FJ . 1998 Oncogene 17: 1625–1628

  • DeCaprio JA, Ludlow JW, Lynch D, Furukawa Y, Griffin J, Piwnica-Worms H, Huang CM, Livingston DM . 1989 Cell 58: 1085–1095

  • Dowdy SF, Hinds PW, Louie K, Reed SI, Arnold A, Weinberg RA . 1993 Cell 73: 499–511

  • Easton J, Wei T, Lahti JM, Kidd VJ . 1998 Cancer Res. 58: 2624–2632

  • Eng C, Herman JG, Baylin SB . 2000 Nat. Genet. 24: 101–102

  • Eng C, Li FP, Abramson DH, Ellsworth RM, Wong FL, Goldman MB, Seddon J, Tarbell N, Boice Jr JD . 1993 J. Natl. Cancer Inst. 85: 1121–1128

  • Ezhevsky SA, Ho A, Becker-Hapak M, Davis PK, Dowdy SF . 2001 Mol. Cell. Biol. 21: 4773–4784

  • Falco JP, Baylin SB, Lupu R, Borges M, Nelkin BD, Jasti RK, Davidson NE, Mabry M . 1990 J. Clin. Invest. 85: 1740–1745

  • Franklin WA, Veve R, Hirsch FR, Helfrich BA, Bunn Jr PA . 2002 Semin. Oncol. 29: 3–14

  • Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM, Dryja TP . 1986 Nature 323: 643–646

  • Gallie BL, Hei YJ, Mostachfi H, Dunn JM . 1995 Molecular Genetics of Cancer Cowell JK (ed) Oxford: Bios Scientific Publishers, Limited pp 1–30

    Google Scholar 

  • Gazdar AF, Bunn Jr PA, Minna JD, Baylin SB . 1985 Science 229: 679–680

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

  • Gray SG, Guo X, Kedra D, Teh BT, Min HQ . 2001 Cancer Res. 61: 5950–5953

  • Grimison B, Langan TA, Sclafani RA . 2000 Cell Growth Differ. 11: 507–515

  • Harbour JW, Dean DC . 2000 Genes Dev. 14: 2393–2409

  • Harbour JW, Lai SL, Whang-Peng J, Gazdar AF, Minna JD, Kaye FJ . 1988 Science 241: 353–357

  • Harvey M, Vogel H, Lee EY, Bradley A, Donehower LA . 1995 Cancer Res. 55: 1146–1151

  • Helin K, Holm K, Niebuhr A, Eiberg H, Tommerup N, Hougaard S, Poulsen HS, Spang-Thomsen M, Norgaard P . 1997 Proc. Natl. Acad. Sci. USA 94: 6933–6938

  • Herman JG, Merlo A, Mao L, Lapidus RG, Issa J-PJ, Davidson NE, Sidransky D, Baylin SB . 1995 Cancer Res. 55: 4525–4530

  • Hirsch FR, Franklin WA, Veve R, Varella-Garcia M, Bunn Jr PA . 2002 Semin. Oncol. 29: 51–58

  • Ho A, Dowdy SF . 2002 Curr. Opin. Genet. Dev. 12: 47–52

  • Horowitz JM, Park SH, Bogenmann E, Cheng JC, Yandell DW, Kaye FJ, Minna JD, Dryja TP, Weinberg RA . 1990 Proc. Natl. Acad. Sci. USA 87: 2775–2779

  • Jacks T, Fazeli A, Schmitt EM, Bronson RT, Goodell MA, Weinberg RA . 1992 Nature 359: 295–300

  • Jiang H, Chou HS, Zhu L . 1998 Mol. Cell. Biol. 18: 5284–5290

  • Johnson BE, Makuch RW, Simmons AD, Gazdar AF, Burch D, Cashell AW . 1988 Cancer Res. 48: 5163–5166

  • Kaelin Jr W, Krek W, Sellers WR, DeCaprio JA, Ajchenbaum F, Fuchs CS, Chittenden T, Li Y, Farnham PJ, Blanar MA, Livingston DM, Flemington EK . 1992 Cell 70: 351–364

  • Kaelin Jr W, Pallas DC, DeCaprio JA, Kaye FJ, Livingston DM . 1991 Cell 64: 521–532

  • Kamb A, Gruis NA, Weaver-Feldhaus J, Liu Q, Harshman K, Tavtigian SV, Stockert E, Day RR, Johnson BE, Skolnick MH . 1994 Science 264: 436–440

  • Kaye F, Kubo A . 2001 Molecular Genetics of Cancer 2nd edn Cowell JK (ed) Oxford: Bios Scientific Publishers Ltd pp. 387–413

    Google Scholar 

  • Kaye FJ, Kratzke RA, Gerster JL, Horowitz JM . 1990 Proc. Natl. Acad. Sci. USA 87: 6922–6926

  • Kelley MJ, Nakagawa K, Steinberg SM, Mulshine JL, Kamb A, Johnson BE . 1995a J. Natl. Cancer Inst. 87: 756–761

  • Kelley MJ, Otterson GA, Kaye FJ, Popescu NC, Johnson BE, Dipaolo JA . 1995b Int. J. Cancer 63: 226–230

  • Kleinerman RA, Tarone RE, Abramson DH, Seddon JM, Li FP, Tucker MA . 2000 J. Natl. Cancer Inst. 92: 2037–2039

  • Koh J, Enders GH, Dynlacht BD, Harlow E . 1995 Nature 375: 506–510

  • Kohno T, Yokota J . 1999 Carcinogenesis 20: 1403–1410

  • Kratzke RA, Shimizu E, Geradts J, Gerster JL, Segal S, Otterson GA, Kaye FJ . 1993 Cell Growth Differ. 4: 629–635

  • Lee EY, Chang CY, Hu N, Wang YC, Lai CC, Herrup K, Lee WH, Bradley A . 1992 Nature 359: 288–294

  • Lee WH, Murphree AL, Benedict WF . 1984 Nature 309: 458–460

  • Lee WH, Shew JY, Hong FD, Sery TW, Donoso LA, Young LJ, Bookstein R, Lee EY . 1987 Nature 329: 642–645

  • Lipinski MM, Jacks T . 1999 Oncogene 18: 7873–7882

  • Ludlow JW, DeCaprio JA, Huang CM, Lee WH, Paucha E, Livingston DM . 1989 Cell 56: 57–65

  • Merlo A, Herman JG, Mao L, Lee DJ, Gabrielson E, Burger PC, Baylin SB, Sidransky D . 1995 Nat. Med. 1: 686–692

  • Mihara K, Cao XR, Yen A, Chandler S, Driscoll B, Murphree AL, T'Ang A, Fung YK . 1989 Science 246: 1300–1303

  • Mitsudomi T, Viallet J, Mulshine JL, Linnoila RI, Minna JD, Gazdar AF . 1991 Oncogene 6: 1353–1362

  • Modi S, Kubo A, Oie H, Coxon AB, Rehmatulla A, Kaye FJ . 2000 Oncogene 19: 4632–4639

  • Momparler RL, Ayoub J . 2001 Lung Cancer 34: Suppl 4 S111–S115

  • Morris EJ, Dyson NJ . 2001 Adv. Cancer Res. 82: 1–54

  • Nau MM, Brooks Jr B, Carney DN, Gazdar AF, Battey JF, Sausville EA, Minna JD . 1986 Proc. Natl. Acad. Sci. USA 83: 1092–1096

  • Nevins JR . 1998 Cell Growth Differ. 9: 585–593

  • Nuovo GJ, Plaia TW, Belinsky SA, Baylin SB, Herman JG . 1999 Proc. Natl. Acad. Sci. USA 96: 12754–12759

  • Ookawa K, Shiseki M, Takahashi R, Yoshida Y, Terada M, Yokota J . 1993 Oncogene 8: 2175–2181

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

  • Otterson GA, Khleif SN, Chen W, Coxon AB, Kaye FJ . 1995 Oncogene 11: 1211–1216

  • Otterson GA, Kratzke RA, Coxon A, Kim YW, Kaye FJ . 1994 Oncogene 9: 3375–3378

  • Park IW, Wistuba II, Maitra A, Milchgrub S, Virmani AK, Minna JD, Gazdar AF . 1999 J. Natl. Cancer Inst. 91: 1863–1868

  • Parry D, Bates S, Mann DJ, Peters G . 1995 EMBO J. 14: 503–511

  • Sanders BM, Jay M, Draper GJ, Roberts EM . 1989 Br. J. Cancer 60: 358–365

  • Sears RC, Nevins JR . 2002 J. Biol. Chem. 277: 11617–11620

  • Sellers WR, Kaelin Jr WG . 1997 J. Clin. Oncol. 15: 3301–3312

  • Senderowicz AM, Sausville EA . 2000 J. Natl. Cancer Inst. 92: 376–387

  • Serrano M, Hannon GJ, Beach D . 1993 Nature 366: 704–707

  • Shapiro GI, Edwards CD, Kobzik L, Godleski J, Richards W, Sugarbaker DJ, Rollins BJ . 1995 Cancer Res. 55: 505–509

  • Sherr CJ . 2001 Nat. Rev. Mol. Cell. Biol. 2: 731–737

  • Sherr CJ, Roberts JM . 1999 Genes Dev. 13: 1501–1512

  • Shimizu E, Coxon A, Otterson GA, Steinberg SM, Kratzke RA, Kim YW, Fedorko J, Oie H, Johnson BE, Mulshine JL, Minna JD, Gazdar AF, Kaye FJ . 1994 Oncogene 9: 2441–2448

  • Spruck CR, Gonzalez-Zulueta M, Shibata A, Simoneau AR, Lin MF, Gonzales F, Tsai YC, Jones PA . 1994 Nature 370: 183–184

  • Sugio K, Kishimoto Y, Virmani AK, Hung JY, Gazdar AF . 1994 Cancer Res. 54: 5811–5815

  • Tomizawa Y, Adachi J, Kohno T, Yamaguchi N, Saito R, Yokota J . 1998 Jpn. J. Clin. Oncol. 28: 192–195

  • Weinberg RA . 1995 Cell 81: 323–330

  • Weiser TS, Guo ZS, Ohnmacht GA, Parkhurst ML, Tong-On P, Marincola FM, Fischette MR, Yu X, Chen GA, Hong JA, Stewart JH, Nguyen DM, Rosenberg SA, Schrump DS . 2001 J. Immunother. 24: 151–161

  • Williams BO, Remington L, Albert DM, Mukai S, Bronson RT, Jacks T . 1994 Nat. Genet. 7: 480–484

  • Yokota J, Akiyama T, Fung YK, Benedict WF, Namba Y, Hanaoka M, Wada M, Terasaki T, Shimosato Y, Sugimura T, Terada M . 1988 Oncogene 3: 471–475

  • Yokota J, Wada M, Shimosato Y, Terada M, Sugimura T . 1987 Proc. Natl. Acad. Sci. USA 84: 9252–9256

  • Yu Q, Geng Y, Sicinski P . 2001 Nature 411: 1017–1021

  • Zalvide J, Stubdal H, DeCaprio JA . 1998 Mol. Cell. Biol. 18: 1408–1415

  • Zochbauer-Muller S, Gazdar AF, Minna JD . 2002 Annu. Rev. Physiol. 64: 681–708

Download references

Author information

Authors and Affiliations

  1. Genetics Branch, Center for Cancer Research, NCI, NIH and National Naval Medical Center, Bethesda, MD 20889, Maryland, USA

    Frederic J Kaye

Authors
  1. Frederic J Kaye
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Frederic J Kaye.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kaye, F. RB and cyclin dependent kinase pathways: defining a distinction between RB and p16 loss in lung cancer. Oncogene 21, 6908–6914 (2002). https://doi.org/10.1038/sj.onc.1205834

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205834

Keywords

This article is cited by

Search

Advanced search

Quick links