Skip to main content
SpringerLink
Log in

PTEN: History of a Tumor Suppressor

  • Protocol
  • First Online:
PTEN

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1388))

Abstract

Starting from the discovery of “inhibitory chromosomes” by Theodor Boveri to the finding by Henry Harris that fusing a normal cell to a cancer cell reduced tumorigenic potential, the notion of tumor suppression was recognized well before any tumor-suppressor genes were discovered. Although not the first to be revealed, PTEN has been demonstrated to be one of the most frequently altered tumor suppressors in cancer. This introductory chapter provides a historical perspective on our current understanding of PTEN including some of the seminal discoveries in the tumor suppressor field, the events leading to PTEN’s discovery, and an introduction to some of the most important researchers and their studies which have shed light on PTEN biology and function as we know it today.

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

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover 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

References

  1. Boveri T (1914) In Zur Frage der Entstehung Maligner Tumoren. Gustav Fischer, Jena, pp 1–64

    Google Scholar 

  2. Boveri T (2008) Concerning the origin of malignant tumours by Theodor Boveri. translated and annotated by Henry Harris. J Cell Sci 121(Suppl 1):1–84. doi:10.1242/jcs.025742

    Article  PubMed  Google Scholar 

  3. Harris H, Miller OJ, Klein G et al (1969) Suppression of malignancy by cell fusion. Nature 223:363–368. doi:10.1038/223363a0

    Article  CAS  PubMed  Google Scholar 

  4. Knudson AG (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A 68:820–823. doi:10.1073/pnas.68.4.820

    Article  PubMed  PubMed Central  Google Scholar 

  5. Yunis JJ, Ramsay N (1978) Retinoblastoma and subband deletion of chromosome 13. Am J Dis Child 132:161–163. doi:10.1001/archpedi.1978.02120270059012

    Article  CAS  PubMed  Google Scholar 

  6. Cavenee WK, Dryja TP, Phillips RA et al (1983) Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature 305:779–784

    Article  CAS  PubMed  Google Scholar 

  7. Lee WH, Bookstein R, Hong F et al (1987) Human retinoblastoma susceptibility gene: cloning, identification, and sequence. Science 235:1394–1399. doi:10.1126/science.3823889

    Article  CAS  PubMed  Google Scholar 

  8. Baker SJ, Markowitz S, Fearon ER et al (1990) Suppression of human colorectal carcinoma cell growth by wild-type p53. Science 249:912–915

    Article  CAS  PubMed  Google Scholar 

  9. Haber DA, Buckler AJ, Glaser T et al (1990) An internal deletion within an 11p13 zinc finger gene contributes to the development of Wilms’ tumor. Cell 61:1257–1269

    Article  CAS  PubMed  Google Scholar 

  10. Call KM, Glaser T, Ito CY et al (1990) Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms’ tumor locus. Cell 60:509–520

    Article  CAS  PubMed  Google Scholar 

  11. Fearon ER, Cho KR, Nigro JM et al (1990) Identification of a chromosome 18q gene that is altered in colorectal cancers. Science 247:49–56

    Article  CAS  PubMed  Google Scholar 

  12. Hall JM, Lee MK, Newman B et al (1990) Linkage of early-onset familial breast cancer to chromosome 17q21. Science 250:1684–1689

    Article  CAS  PubMed  Google Scholar 

  13. Narod SA, Feunteun J, Lynch HT et al (1991) Familial breast-ovarian cancer locus on chromosome 17q12-q23. Lancet 338:82–83

    Article  CAS  PubMed  Google Scholar 

  14. Carter BS, Ewing CM, Ward WS et al (1990) Allelic loss of chromosomes 16q and 10q in human prostate cancer. Proc Natl Acad Sci U S A 87:8751–8755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sonoda Y, Murakami Y, Tominaga T et al (1996) Deletion mapping of chromosome 10 in human glioma. Jpn J Cancer Res 87:363–367

    Article  CAS  PubMed  Google Scholar 

  16. Murakami YS, Albertsen H, Brothman AR et al (1996) Suppression of the malignant phenotype of human prostate cancer cell line PPC-1 by introduction of normal fragments of human chromosome 10. Cancer Res 56:2157–2160

    CAS  PubMed  Google Scholar 

  17. Fujimoto M, Fults DW, Thomas GA et al (1989) Loss of heterozygosity on chromosome 10 in human glioblastoma multiforme. Genomics 4:210–214. doi:10.1016/0888-7543(89)90302-9

    Article  CAS  PubMed  Google Scholar 

  18. Bigner SH, Mark J, Mahaley MS, Bigner DD (1984) Patterns of the early, gross chromosomal changes in malignant human gliomas. Hereditas 101:103–113

    Article  CAS  PubMed  Google Scholar 

  19. Li J, Yen C, Liaw D et al (1997) PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275:1943–1947

    Article  CAS  PubMed  Google Scholar 

  20. Steck PA, Pershouse MA, Jasser SA et al (1997) Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet 15:356–362. doi:10.1038/ng0497-356

    Article  CAS  PubMed  Google Scholar 

  21. Liaw D, Marsh DJ, Li J et al (1997) Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet 16:64–67. doi:10.1038/ng0597-64

    Article  CAS  PubMed  Google Scholar 

  22. Li DM, Sun H (1997) TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta. Cancer Res 57:2124–2129

    CAS  PubMed  Google Scholar 

  23. Wang SI, Puc J, Li J et al (1997) Somatic mutations of PTEN in glioblastoma multiforme. Cancer Res 57:4183–4186

    CAS  PubMed  Google Scholar 

  24. Cairns P, Okami K, Halachmi S et al (1997) Frequent inactivation of PTEN/MMAC1 in primary prostate cancer. Cancer Res 57:4997–5000

    CAS  PubMed  Google Scholar 

  25. Guldberg P, Thor Straten P, Birck A et al (1997) Disruption of the MMAC1/PTEN gene by deletion or mutation is a frequent event in malignant melanoma. Cancer Res 57:3660–3663

    CAS  PubMed  Google Scholar 

  26. Tashiro H, Blazes MS, Wu R et al (1997) Mutations in PTEN are frequent in endometrial carcinoma but rare in other common gynecological malignancies. Cancer Res 57:3935–3940

    CAS  PubMed  Google Scholar 

  27. Risinger JI, Hayes AK, Berchuck A, Barrett JC (1997) PTEN/MMAC1 mutations in endometrial cancers. Cancer Res 57:4736–4738

    CAS  PubMed  Google Scholar 

  28. Rasheed BK, Stenzel TT, McLendon RE et al (1997) PTEN gene mutations are seen in high-grade but not in low-grade gliomas. Cancer Res 57:4187–4190

    CAS  PubMed  Google Scholar 

  29. Dahia PL, Marsh DJ, Zheng Z et al (1997) Somatic deletions and mutations in the Cowden disease gene, PTEN, in sporadic thyroid tumors. Cancer Res 57:4710–4713

    CAS  PubMed  Google Scholar 

  30. Marsh DJ, Dahia PL, Zheng Z et al (1997) Germline mutations in PTEN are present in Bannayan-Zonana syndrome. Nat Genet 16:333–334. doi:10.1038/ng0897-333

    Article  CAS  PubMed  Google Scholar 

  31. Nelen MR, van Staveren WC, Peeters EA et al (1997) Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease. Hum Mol Genet 6:1383–1387

    Article  CAS  PubMed  Google Scholar 

  32. Arch EM, Goodman BK, Van Wesep RA et al (1997) Deletion of PTEN in a patient with Bannayan-Riley-Ruvalcaba syndrome suggests allelism with Cowden disease. Am J Med Genet 71:489–493

    Article  CAS  PubMed  Google Scholar 

  33. Lynch ED, Ostermeyer EA, Lee MK et al (1997) Inherited mutations in PTEN that are associated with breast cancer, cowden disease, and juvenile polyposis. Am J Hum Genet 61:1254–1260. doi:10.1086/301639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Myers MP, Stolarov JP, Eng C et al (1997) P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase. Proc Natl Acad Sci U S A 94:9052–9057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Furnari FB, Lin H, Huang HS, Cavenee WK (1997) Growth suppression of glioma cells by PTEN requires a functional phosphatase catalytic domain. Proc Natl Acad Sci U S A 94:12479–12484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Myers MP, Tonks NK (1997) PTEN: sometimes taking it off can be better than putting it on. Am J Hum Genet 61:1234–1238. doi:10.1086/301659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Maehama T, Dixon JE (1998) The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 273:13375–13378

    Article  CAS  PubMed  Google Scholar 

  38. Carpenter CL, Cantley LC (1996) Phosphoinositide kinases. Curr Opin Cell Biol 8:153–158. doi:10.1016/S0955-0674(96)80060-3

    Article  CAS  PubMed  Google Scholar 

  39. Myers MP, Pass I, Batty IH et al (1998) The lipid phosphatase activity of PTEN is critical for its tumor suppressor function. Proc Natl Acad Sci U S A 95:13513–13518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Tamura M, Gu J, Matsumoto K et al (1998) Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science 280:1614–1617

    Article  CAS  PubMed  Google Scholar 

  41. Gu J, Tamura M, Yamada KM (1998) Tumor suppressor PTEN inhibits integrin- and growth factor-mediated mitogen-activated protein (MAP) kinase signaling pathways. J Cell Biol 143:1375–1383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Zhang XC, Piccini A, Myers MP et al (2012) Functional analysis of the protein phosphatase activity of PTEN. Biochem J 444:457–464. doi:10.1042/BJ20120098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Di Cristofano A, Pesce B, Cordon-Cardo C, Pandolfi PP (1998) Pten is essential for embryonic development and tumour suppression. Nat Genet 19:348–355. doi:10.1038/1235

    Article  PubMed  Google Scholar 

  44. Stambolic V, Suzuki A, de la Pompa JL et al (1998) Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 95:29–39. doi:10.1016/S0092-8674(00)81780-8

    Article  CAS  PubMed  Google Scholar 

  45. Suzuki A, de la Pompa JL, Stambolic V et al (1998) High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice. Curr Biol 8:1169–1178. doi:10.1016/S0960-9822(07)00488-5

    Article  CAS  PubMed  Google Scholar 

  46. Podsypanina K, Ellenson LH, Nemes A et al (1999) Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems. Proc Natl Acad Sci U S A 96:1563–1568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Lee JO, Yang H, Georgescu MM et al (1999) Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association. Cell 99:323–334

    Article  CAS  PubMed  Google Scholar 

  48. Worby CA, Dixon JE (2014) PTEN. Annu Rev Biochem 83:641–669. doi:10.1146/annurev-biochem-082411-113907

    Article  CAS  PubMed  Google Scholar 

  49. Berger AH, Knudson AG, Pandolfi PP (2011) A continuum model for tumour suppression. Nature 476:163–169. doi:10.1038/nature10275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Trotman LC, Niki M, Dotan ZA et al (2003) Pten dose dictates cancer progression in the prostate. PLoS Biol 1:E59. doi:10.1371/journal.pbio.0000059

    Article  PubMed  PubMed Central  Google Scholar 

  51. Alimonti A, Carracedo A, Clohessy JG et al (2010) Subtle variations in Pten dose determine cancer susceptibility. Nat Genet 42:454–458. doi:10.1038/ng.556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Salmena L, Carracedo A, Pandolfi PP (2008) Tenets of PTEN tumor suppression. Cell 133:403–414. doi:10.1016/j.cell.2008.04.013

    Article  CAS  PubMed  Google Scholar 

  53. Bassi C, Stambolic V (2013) PTEN, here, there, everywhere. Cell Death Differ 20:1595–1596. doi:10.1038/cdd.2013.127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Hopkins BD, Hodakoski C, Barrows D et al (2014) PTEN function: the long and the short of it. Trends Biochem Sci 39:183–190. doi:10.1016/j.tibs.2014.02.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Song MS, Salmena L, Pandolfi PP (2012) The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol 13:283–296. doi:10.1038/nrm3330

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The research in the author’s lab is supported by funds from Canada Research Chairs, Human Frontier Science Program Organization, Leukemia and Lymphoma Society of Canada, Canadian Cancer Society, and the Natural Sciences and Engineering Research Council of Canada. Critical reading by J. Kotsopoulos and J.F. Woolley is greatly appreciated.

Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, University of Toronto, Princess Margaret Cancer Centre, Room 4211, Medical Sciences Building, 1 King’s College Circle, Toronto, ON, Canada, M5S 1A8

    Leonardo Salmena

Authors
  1. Leonardo Salmena
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Leonardo Salmena .

Editor information

Editors and Affiliations

  1. University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada

    Leonardo Salmena

  2. University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada

    Vuk Stambolic

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this protocol

Cite this protocol

Salmena, L. (2016). PTEN: History of a Tumor Suppressor. In: Salmena, L., Stambolic, V. (eds) PTEN. Methods in Molecular Biology, vol 1388. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3299-3_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-3299-3_1

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3297-9

  • Online ISBN: 978-1-4939-3299-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation