Skip to main content
SpringerLink
Log in

p16 Family Inhibitors of Cyclin-Dependent Kinases

  • Chapter
Cancer Genes

Part of the book series: Pezcoller Foundation Symposia ((PFSO,volume 7))

  • 49 Accesses

Abstract

The origin and development of human tumors begins at the molecular level and involves a complex multi-step process. A feature common to many tumor cells is their ability to enter and progress through the cell division cycle under conditions where normal cells would either be quiescent or proliferating at a reduced rate. Therefore, the molecular pathways controlling the cell division cycle must inevitably interact with pathways which regulate cell growth, and are a very likely target of oncogenic events. It was not until very recently, however, that experimental evidence became available to bring such a connection to light.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 16.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Afshari, C. A., M. A. Nichols, Y. Xiong, and M. Mudryj. The p2 1 protein interacts with multiple E2F complexes during the cell cycle. submitted (1994)

    Google Scholar 

  2. Andrews, B. J. and I. Herskowitz. The yeast SWI4 protein contains a motif present in developmental regulators and is part of a complex involved in cell-cycle dependent transcription.. Nature 342: 830–833 (1989)

    Article  PubMed  CAS  Google Scholar 

  3. Aprelikova, O.,Y. XIONG, and E. T. Liu. Both p16 and p21 families of CDK phosphorylatio bt the CDK activating kinase(CAK). J. Biol. Chem. in press:(1995)

    Google Scholar 

  4. Baker, S. J., E. R. Fearon, J. M. Nigro, S. R. Hamilton, A. C. Preisinger, J. M. Jessus, P. van Tuinen, D. H. Ledbetter, D. F. Barker, Y. Nakamura, R. White, and B. Vogelstein. Chromosome 17 deletions and p53 gene mutations in colorectal carcinoma. Science 244: 217–221 (1989)

    Article  PubMed  CAS  Google Scholar 

  5. Bartel, P. L., C. -T. Chien, R. Sternglanz, and S. Fields. 1993. Using the two hybrid system to detect protein-protein interactions, p. 153–179. In D. A. Hartley (ed.), Cellular Interactions in Development: A Practical Approach. Oxford University Press, Oxford, UK.

    Google Scholar 

  6. Bates, S., D. Parry, L. Bonetta, K. Vousden, C. Dickson, and G. Peters. Absence of cyclin D/cdk complexes in cells lacking functional retinoblastoma protein. Oncogene 9: 1633–1640 (1994)

    PubMed  CAS  Google Scholar 

  7. Bierkamp, C. and J. A. Campos-Ortega. A zebrafish homologue of the Drosophila neurogenic gene Notch and its pattern of transcription during early embryogenesis. Mech. Dey. 43: 87–100 (1993)

    Article  CAS  Google Scholar 

  8. Boukamp, P., R. T. Petrussevska, D. Breitkreutz, J. Hornung, A. Markham, and N. E. Fusenig. Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. J. Cell Biol. 106: 761–771 (1988)

    Article  PubMed  CAS  Google Scholar 

  9. Breeden, L. and K. Nasmyth. Similarity between cell-cycle genes of budding yeast and fission yeast and the Notch gene of Drosophila. Nature 329: 651–654 (1987)

    Article  PubMed  CAS  Google Scholar 

  10. Caldas, C., S. A. Hahn, L. T. da Costa, M. S. Redston, M. Schutte, A. B. Seymour, C. L. Weinstein, R. H. Hruban, C. J. Yeo, and S. E. Kern. Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma. Nature Genet. 8: 27–32 (1994)

    Article  PubMed  CAS  Google Scholar 

  11. Coffman, C., W. Harris, and C. Kintner. Xotch, the xenopus homolog of Drosophila notch. Science 249: 1438–1441 (1990)

    Article  PubMed  CAS  Google Scholar 

  12. Datto, M. B., Y. Li, J. F. Panus, D. J. Howe, Y. Xiong, and X-F. Wang. TGF-β induces the cyclin-dependent kinase inhibitor, p21 through a p53 independent mechanism. Proc. Natl. Acad. Sci. USA in press:(1995)

    Google Scholar 

  13. Dulic, V., W. K. Kaufmann, S. J. Wilson, T. D. Tlsty, E. Lees, J. W. Harper, S. J. Elledge, and S. I. Reed. p53-dependent inhibtion of cyclin-dependent kinase activities in human fibroblasts during radiation-induced GI arrest. Cell 76: 1013–1023 (1994)

    Article  PubMed  CAS  Google Scholar 

  14. Dyson, N., P. M. Howley, K. Munger, and E. Harlow. The human papillomavirus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science 243: 934–937 (1989)

    Article  PubMed  CAS  Google Scholar 

  15. El-Deiry, W. S., T. Tokino, V. E. Velculescu, D. B. Levy, R. Parsons, D. M Lin, W. E. Mercer, K. W. V Kinzler, and B. Vogelstein. WAFT, a potential mediator of p53 tumor suppression. Cell 75: 817–825 (1993)

    Article  PubMed  CAS  Google Scholar 

  16. Ellisen, L. W., J. Bird, D. C. West, A. L. Soreng, T. C. Reynolds, S. D. Smith, and J. Sklar. TAN-1, the human homolog of the Drosophila Notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell 66: 649–661 (1991)

    Article  PubMed  CAS  Google Scholar 

  17. Evans, T., E. T. Rosenthal, J. Youngblom, D. Distel, and T. Hunt. Cyclins: a protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division. Cell 33: 389–396 (1983)

    Article  PubMed  CAS  Google Scholar 

  18. Ewen, M. E. The cell cycle and the retinoblastoma protein family. Cancer and Metastasis Rev. 13: 45–66 (1994)

    Article  CAS  Google Scholar 

  19. Flores-Rozas, H., Z. Kelman, F. B. Dean, Z-Q. Pan, J. W. Harper, S. J. Elledge, M. O’Donell, and J. Hurwitz. Cdk-interacting protein directly binds with proliferating cell nuclear antigen and inhibits DNA replication catalyzed by the DNA polymerase d holoenzyme. Proc. Natl. Acad. Sci. USA 91: 8655–8659 (1994)

    Article  PubMed  CAS  Google Scholar 

  20. Greenwald, I. S. and G. M. Rubin. Making a difference: the role of cell-cell interactions in establishing separate identities for equivalent cells. Cell 68: 271–281 (1992)

    Article  PubMed  CAS  Google Scholar 

  21. Gu, Y., C. W. Turck, and D. O. Morgan. Inhibition of CDK2 activity in vivo by an associated 20K regulatory subunit. Nature 366: 707–710 (1993)

    Article  PubMed  CAS  Google Scholar 

  22. Guan, K-L., C. W. Jenkins, Y. Li, M. A. Nichols, X. Wu, C. L. O’Keefe, A. G. Matera, and Y. Xiong. Growth suppression by p 1 8, a p16INK4/MTS1 - and p14INK4B/MTS2 - related CDK6 inhibitor, correlates with wild-type pRb function. Genes & Dev. 8: 2939–2952 (1994)

    Article  CAS  Google Scholar 

  23. Guan, K. L., C. W. Jenkins, Y. Li, C. L. O’Keefe, S. Noh, X. Wu, M. Zariwala, A. G. Matera, and Y. Xiong. Isolation and characterization of p20, a p16-related inhibitor specific to CDK6 and CDK4. submitted (1995)

    Google Scholar 

  24. Halevy, O., B. G. Novitch, D. B. Spicer, S. X. Skapek, J. Rhee, G. J. Hannon, D. Beach, and A. B. Lassar. Terminal cell cycle arrest of skeletal muscle correlates with induction of p21 by MyoD. Science 267: 1018–1021 (1995)

    Article  PubMed  CAS  Google Scholar 

  25. Hannon, G. J. and D. Beach. P15INK4B is a potential effector of TGF-β-induced cell cycle arrest. Nature 371: 257–261 (1994)

    Article  PubMed  CAS  Google Scholar 

  26. Harper, J. W., G. R. Adami, N. Wei, K. Keyomarsi, and S. J. Elledge. The p21 cdk-interacting protein cipl is a potent inhibitor of G1 cyclin-dependent kinases. Cell 75: 805–816 (1993)

    Article  PubMed  CAS  Google Scholar 

  27. Hartwell, L. Defects in a cell cycle checkpoint may be responsihle for the genomic instability of cancer cells. Cell 71: 543–546 (1992)

    Article  PubMed  CAS  Google Scholar 

  28. Hinds, P. W., S. Mittnacht, V. Dulic, A. Arnold, S. I. Reed, and R. A. Weinberg. Regulation of retinoblastoma protein functions by ectopic expression of human cyclins. Cell 70: 993–1006 (1992)

    Article  PubMed  CAS  Google Scholar 

  29. Hollstein, M., D. Sidransky, B. Vogelstein, and C. C. Harris. p53 mutations in human cancers. Science 253: 49–53 (1991)

    Article  PubMed  CAS  Google Scholar 

  30. Hu, Q. -J., C. Bautista, G. M. Edwards, J. D. Defeo, R. E. Jone. and E. Harlow. Antibodies specific for the human retinoblastoma protein identify a family of related polypeptides. Mol. Cell Biol. 11: 5792–5799 (1994)

    Google Scholar 

  31. Hunter, T. and J. Pines. Cyclins and cancer II: cyclin D and CDK inhibitors come of age. Cell 79: 573–582 (1994)

    Article  PubMed  CAS  Google Scholar 

  32. Hussussian, C. J., J. P. Struewing, A. M. Goldstein, P. A. T. Higgins, D. S. Ally, M. D. Sheahan, W. H. Clark, M. A. Tucker, and N. C. Dracopoli. Germline p16 mutations in familial melanoma. Nature Genet. 8: 15–21 (1994)

    Article  PubMed  CAS  Google Scholar 

  33. Inaba, T., H. Matsushime, M. Valentine, M. F. Roussel, C. J. Sherr, and A. T. Look. Genomic organization, chromosomal localization, and independent expression of human cyclin D genes. Genomics 13: 565–574 (1992)

    Article  PubMed  CAS  Google Scholar 

  34. Jiang, H., Z-Z. Su, F. Collart, E. Huberman, and P. Fisher. Induction of differentiation in human promyelocytic HL-60 leukemia cells activates p21, WAFT/CIPI, expression in the absence of p53. Oncogene 9: 3397–3406 (1994)

    PubMed  CAS  Google Scholar 

  35. Kamb, A., N. A. Gruis, J. Weaver-Feldhaus, Q. Liu, K. Harshman, S. V. Tavitgian, E. Stockert, R. S. Day, B. E. Johnson, and M. H. Skolnick. A cell cycle regulator potentially involved in genesis of many tumor types. Science 264: 436 440 (1994)

    Article  PubMed  CAS  Google Scholar 

  36. Kamb, A., D. Shattuck-Eidens, R. Eeles, Q. Liu, N. A. Gruis, W. Ding, C. Hussey, T. Tran, Y. Miki, J. Weaver-Feldhaus, M. McClure, J. F. Aitken, D. E. Anderson, W. Bergman, R. Frants, D. E. Goldgar, A. Green, R. MacLennan, N. G. Martin, L. J. Meyer, P. Youl, J. J. Zone, M. H. Skolnick, and L. A. Cannon-Albright. Analysis of the p16 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus. Nature Genet. 8: 22–26 (1994)

    Article  CAS  Google Scholar 

  37. Kato. J., M. Matsuoka, K. Polyak, J. Massague, and C. J. Sherr. Cyclic AMP-induced GI phase arrest mediated by an inhibitor (p27Kipl) of cyclin-dependent kinase 4 activation. Cell 79: 487–496 (1994)

    Article  PubMed  CAS  Google Scholar 

  38. Lane, D. P. p53, guardian of the genome. Nature 358: 15–16 (1992)

    Article  PubMed  CAS  Google Scholar 

  39. Li, Y., C. W. Jenkins, M. A. Nichols, and Y. Xiong. Cell cycle expression and p53 regulation of the cyclindependent kinase inhibitor p21. Oncogene 9: 2261–2268 (1994)

    PubMed  CAS  Google Scholar 

  40. Li, Y., M. A. Nichols, J. W. Shay, and Y. Xiong. Transcriptional repression of the D-type cyclin-dependent kinases inhibitor p16 by the retinoblastoma susceptibility gene product, pRb. Cancer Res. 54: 6078–6082 (1994)

    PubMed  CAS  Google Scholar 

  41. Lukas, J., H. Muller, J. Bartkova, D. Spitkovsky, A. A. Kjeruff, P. Jansen-Durr, M. Strauss, and J. Bartek. DNA tumor virus oncoproteins and retinoblastoma gene mutations share the ability to relieve the cell’s requirement for cyclin D1 function in Gl. J. Cell Biol. 125: 625–638 (1994)

    Article  PubMed  CAS  Google Scholar 

  42. Meyerson, M., G. H. Enders, C-L. Wu, L-K. Su, C. Gorka, C. Neilson, E. Harlow, and L-H. Tsai. A family of human cdc2-related protein kinases. EMBO J. 11:2909–2917(1992)

    PubMed  CAS  Google Scholar 

  43. Meyerson, M. and E. Harlow. Identification of GI kinase activity for cdk6, a novel cyclin D partner. Mol. Cell Biol. 14: 2077–2086 (1994)

    PubMed  CAS  Google Scholar 

  44. Michieli, P., M. Chedid, D. Lin, J. H. Pierce, E. Mercer, and D. Givol. Induction of WAF1/CIPI by a p53-independent pathway. Cancer Res. 54: 3391–3395 (1994)

    PubMed  CAS  Google Scholar 

  45. Mori, T., K. Miura, T. Aoki, T. Nishihira, N. Shozo, and Y. Nakamura. Frequent somatic mutation of the MTS1/CDK4I (multiple tumor suppressor/cyclin-dependent kinase 4 inhibitor) gene in esophageal squamous cell carcinoma. Cancer Res. 54: 3396–3397 (1994)

    PubMed  CAS  Google Scholar 

  46. Nevins, J. R. E2F: a link between the Rb tumor suppressor protein and viral oncoproteins. Science 258: 424–429 (1992)

    Article  PubMed  CAS  Google Scholar 

  47. Nigro, J. M., S. J. Baker, A. C. Preisinger, J. M. Jessup, R. Hostetter, K. Cleary, S. H. Signer, N. Davison, S. Baylin, P. Devilee, T. Glover, F. Collins, A. Weston, R. Modali, C. C. Harris, and B. Vogelstein. Mutations in the p53 gene occur in diverse human tumor types. Nature 342: 705–708 (1989)

    Article  PubMed  CAS  Google Scholar 

  48. Nobori, T., K. Mlura, D. J. Wu, A. Lois, K. Takabayashi, and D. A. Carson. Deletion of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature 368: 753–756 (1994)

    Article  PubMed  CAS  Google Scholar 

  49. Noda, A., Y. Ning, S. F. Venable, O. M. Pereira-Smith, and J. R. Smith. Cloning of senescent cell-derived inhibitor of DNA synthesis using an expression screen. Exp. Cell. Res. 211: 90–98 (1994)

    Article  PubMed  CAS  Google Scholar 

  50. Parker, S. B., G. Eichele, R Zhang, A. Rawls, A. T. Sands, A. Bradley, E. N. Olson, J. W. Harper, and S. J. Elledge. p53-independent expression of p21Cip1 in muscle and other termnally differentiating cells. Science 267: 1024–1027 (1995)

    Article  PubMed  CAS  Google Scholar 

  51. Parry, D., S. Bates, D. J. Mann, and G. Peters. Lack of cyclin D-Cdk complexes in Rb-negative cells corre-lates with high levels of pl6INK4/MTS1tumour suppressor gene product. EMBO J. 14: 503–511 (1995)

    PubMed  CAS  Google Scholar 

  52. Polyak, K., M-H. Lee, H. Erdjument-Bromage, A. Koff, J. Roberts, R Tempst, and J. Massague. Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. Cell 78: 59–66 (1994)

    Article  PubMed  CAS  Google Scholar 

  53. Schauer, I. E., S. Siriwardana, T. A. Langan, and R. A. Sclafani. Cyclin DI overexpression vs. retinoblastoma inactivation: implications for growth control evasion in non-small cell and small cell lung cancer. Genes Chromosom Cancer 91: 7827–7831 (1994)

    CAS  Google Scholar 

  54. Scheffner, M., B. A. Wemess, J. M. Huibregtse, A. J. Levine, and P. M. Howley. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63: 1129–1136 (1990)

    Article  PubMed  CAS  Google Scholar 

  55. Serrano, M., G. J. Hannon, and D. Beach. A new regulatory motif in cell cycle control causing specific inhibition of cyclin D/CDK4. Nature 366: 704–707 (1993)

    Article  PubMed  CAS  Google Scholar 

  56. Shay, J. W., W. E. Wright, D. Brasiskyte, and B. A. Van Der Haegen. E6 of human papillomavirus type 16 can overcome the M1 stage of immortalization in human mammary epithelial cells but not in human fibroblasts. Oncogene 8: 1407–1413 (1993)

    PubMed  CAS  Google Scholar 

  57. Sherr, C. J. GI phase progression: cycling on cue. Cell 79: 551–555 (1994)

    Article  PubMed  CAS  Google Scholar 

  58. Sherr, C. J. and J. M. Roberts. Inhibitors of mammalian GI cyclin-dependent kinases. Genes & Dev. 9: 1149–1163 (1995)

    Article  CAS  Google Scholar 

  59. Shew, J. Y., B. T. Lin, P. L. Chen, B. Y. Tseng, T. L. Yang-Feng, and W. H. Lee. C-terminal truncation of the retinoblastoma,gene product leads to functional inactivation. Proc. Natl. Acad. Sci. USA 87: 6–10 (1990)

    Article  PubMed  CAS  Google Scholar 

  60. Solomon, M. J. Activation of the various cyclin-cdc2 protein kinases. Current Opin. Cell Biol. 5: 180–186 (1993)

    Article  CAS  Google Scholar 

  61. Spruck III, C. H., M. Gonzalez-Zulueta, A. Shibata, A. R. Simoneau, M-F. Lin, F. Gonzales, Y. C. Tsai, and P. A. Jones. p16 gene in uncultured tumors. Nature 370: 183–184 (1994)

    Article  PubMed  Google Scholar 

  62. Steinman, R. A., B. Hoffman, A. Iro, C. Guillouf, D. A. Liebermann, and M. E. El-houseini. Induction of p21 (WAFT/CIPI) during differentiation. Oncogene 9: 3389–3396 (1994)

    PubMed  CAS  Google Scholar 

  63. Tam, S. W., A. M. Theodoras, J. W. Shay, G. F. Draetta, and M. Pagano. Differential expression and regulation of Cyclin D1 protein in normal and tumor human cells: association with Cdk4 is required for Cyclin D1 function in G1 progression. Oncogene 9: 2663–2674 (1994)

    PubMed  CAS  Google Scholar 

  64. Toyoshima, H. and T. Hunter. p27, a novel inhibitor of GI cyclin-Cdk proteins kinase activity, is related to p21. Cell 78: 67–74 (1994)

    Article  PubMed  CAS  Google Scholar 

  65. Waga, S., G. J. Hannon, D. Beach, and B. Stillman. The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature 369: 574–578 (1994)

    Article  PubMed  CAS  Google Scholar 

  66. Wharton, K. A., K. M. Johansen, T. Xu, and S. Artavanis-Tsakonas. Nucleotide sequence from the neuro-genic locus notch implies a gene product that shares homology with proteins containing EGF-like repeats. Cell 43: 567–581 (1985)

    Article  PubMed  CAS  Google Scholar 

  67. Won, K. A., Y. Xiong, D. Beach, and M. Z. Gilman. Growth-regulated expression of D-type cyclin genes in human diploid fibroblasts. Proc. Natl. Acad. Sci. USA 89: 9910–9914 (1992)

    Article  PubMed  CAS  Google Scholar 

  68. Xiong, Y. and D. Beach. Population explosion in the cyclin family. Current Biol. 1: 362–364 (1991)

    Article  CAS  Google Scholar 

  69. Xiong, Y., G. Hannon, H. Zhang, D. Casso, R. Kobayashi, and D. Beach. p21 is a universal inhibitor of the cyclin kinases. Nature 366: 701–704 (1993)

    Article  PubMed  CAS  Google Scholar 

  70. Xiong, Y., H. Zhang, and D. Beach. D-type cyclins associated with multiple protein kinases and the DNA replication and repair factor PCNA. Cell 71: 505–514 (1992)

    Article  PubMed  CAS  Google Scholar 

  71. Xiong, Y., H. Zhang, and D. Beach. Subunit rearrangement of cyclin-dependent kinases is associated with cellular transformation. Genes & Dev. 7: 1572–1583 (1993)

    Article  CAS  Google Scholar 

  72. Zhang, H., Y. Xiong, and D. Beach. Proliferating cell nuclear antigen and p21 are components of multiple cell cycle kinase complexes. Mol. Biol. Cell 4: 897–906 (1993)

    PubMed  CAS  Google Scholar 

  73. Zhu, L., S. van den Heuvel, K. Helin, A. Fattaey, M. Ewen, D. Livingston, N. Dyson, and E. Harlow. Inhibition of cell proliferation by p107, a relative of the retinoblastoma protein. Genes & Dev. 7: 1111–1125 (1993)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599-3280, USA

    Yan Li & Yue Xiong

  2. Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599-3280, USA

    Christopher W. Jenkins, Michael A. Nichols & Yue Xiong

  3. Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599-3280, USA

    Yue Xiong

  4. The Program in Molecular Biology and Biotechnology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599-3280, USA

    Yue Xiong

  5. Department of Biological Chemistry and Institute of Gerontology, The University of Michigan, Ann Arbor, Michigan, 48109-0606, USA

    Xiaoyu Wu & Kun-Liang Guan

Authors
  1. Yan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christopher W. Jenkins
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael A. Nichols
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaoyu Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kun-Liang Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yue Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Roswell Park Cancer Institute, Buffalo, New York, USA

    Enrico Mihich

  2. MIT Center for Cancer Research, Cambridge, Massachusetts, USA

    David Housman

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer Science+Business Media New York

About this chapter

Cite this chapter

Li, Y., Jenkins, C.W., Nichols, M.A., Wu, X., Guan, KL., Xiong, Y. (1996). p16 Family Inhibitors of Cyclin-Dependent Kinases. In: Mihich, E., Housman, D. (eds) Cancer Genes. Pezcoller Foundation Symposia, vol 7. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5895-8_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-5895-8_4

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7704-7

  • Online ISBN: 978-1-4615-5895-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation