Skip to main content

The Impact of Molecular Genetics on Cancer Research

  • Chapter
Molecular Oncology and Clinical Applications

Part of the book series: MCBU Molecular and Cell Biology Updates ((MCBU))

  • 59 Accesses

Summary

In this review I analyze the role of gene alterations in cancer initiation and progression. The analysis is directed especially at the suppressor genes, because their behaviour gives interesting clues for understanding the molecular mechanisms of cancer. This analysis will lead to a general model for the role of genes in cancers.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
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

  • AlemĂ , S. , Casalbore, P. , Agostini, E. , and Tatò, F. (1985) Differentiation of PC12 phaechromocytoma cells induced by the v-srconcogene. Nature 316:557–559.

    Article  Google Scholar 

  • Buchkovich, K. , Duffy, L. A. , and Harlow, E. (1989) The retinoblastoma protein is phosphorylated during specific phases of the cell cycle. Cell58:1097–1105.

    Article  Google Scholar 

  • Chellappan, S. P. , Hiebert, S. , Mudryj, M. , Horowitz, J. M. , and Nevins, J. R. (1991) The E2F transcription factor is a cellular traget for the RB protein. Cell 65:1053–1061.

    Article  Google Scholar 

  • Crook, T. and Vousden, K. H. (1992) Properties of p53 mutations detected in primary and secondary cervic al cancers suggest mechanisms of metastasis and involvement of environmental carcinogens. EMBOJ.11:3935–3940.

    Google Scholar 

  • Davidoff, A. M. , Iglehart, J. D. , and Marks, J. R. (1992) Immune response to p53 is dependent upon p53/HSP70 complexes in breast cancers. Proc. Natl. Acad. Sei. USA 89:3439–3442.

    Article  Google Scholar 

  • Donehower, L. A. (1992) Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 356:215–221.

    Article  Google Scholar 

  • Farmer, G. , Bargonetti, J. , Zhu, H. , Friedman, P. , Prywes, R. , and Prives, C. (1992) Wild-typ p53 activates transcription in vitro. Nature 358:83–86.

    Article  Google Scholar 

  • Gannon, J. V. , Greaves, R. , Iggo, R. , and Lane, D. P. (1990) Activating mutations in p53 produce a common conformational effect. A monoclonal antibody specific for the mutant form. EMBO J.9:1595–1602.

    Google Scholar 

  • Gilman, A. G. (1987) G proteins: transducers of receptor-generated signals. Ann. Rev. Biochem.56:615–649.

    Article  Google Scholar 

  • Goodrich, D. W. and Lee, W. -H. (1992) Abrogation by c-mycof Gl phase arrest induced by RBprotein but not by p53. Nature 360:177–179.

    Article  Google Scholar 

  • Henderson, S. , Rowe, M. , Gregory, C. , Croom-Carter, D. , Wang, F. , Longnecker, R. , Kieff, E. , and Rickinson, A. (1991) Induction of bcl-2expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death. Cell 65:1107–1115.

    Article  Google Scholar 

  • Kastan, M. B. , Onyekwere, O. , Sidransky, D. , Vogelstein, B. , and Craig, R. W. (1991) Participation of p53 protein in the cellular response to DNA damage. Cancer Res.51:6304–6311.

    Google Scholar 

  • Kastan, M. B. , Zhan, Q. , El-Deiry, W. S. , Carrier, F. , Jacks, T. , Walsh, W. V. , Plunkett, B. S. , Vogelstein, B. , and Fornace, Jr. , A. J. (1992) A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45is defective in Ataxia-Telangiectasia. Cell 10:587–597.

    Article  Google Scholar 

  • Lee, E. Y. -H. P. , Chang, C. -Y. , Hu, N. , Wang, Y. -C. J. , Lai, C. -C. , Herrup, K. , Lee, W. -H. , and Bradley, A. (1992) Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis. Nature 359:288–294.

    Article  Google Scholar 

  • Lin, D. , Shields, M. T. , Ullrich, S. J. , Appella, E. , and Mercer, W. E. (1992) Growth arrest induced by wild-type p53 protein blocks cells prior to or near the restriction point in late G1 phase. Proc. Natl. Acad/Sci. USA 89:9210–9214.

    Article  Google Scholar 

  • Livingstone, L. R. , White, A. , Sprouse, J. , Livanos, E. , Jacks, T. , and Tlsty, T. D. (1992) Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53. Cell 70:923–935.

    Article  Google Scholar 

  • Marshall, C. J. (1991) Tumor suppressor genes. Cell 64:313–326.

    Article  Google Scholar 

  • Moll, U. M. , Riou, G. , and Levine, A. J. (1992) Two distinct mechanisms alter p53 in breast cancer: mutation and nuclear exclusion. Proc. Natl. Acad. Sei. USA 89:7262–7266.

    Article  Google Scholar 

  • Momand, J. , Zambetti, G. P. , Olson, D. C. , George, D. , and Levine, A. J. (1992) The mem-2oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69:1237–1245.

    Article  Google Scholar 

  • Murray, A. W. (1992) Creative blocks: cell-cycle checkpoints and feedback controls. Nature 359:599–604.

    Article  Google Scholar 

  • Nevins, J. R. (1992) E2F: A link between the Rb tumor suppressor protein and viral oncoproteins. Science258:424–429.

    Article  Google Scholar 

  • Oliner, J. D. , Kinzler, K. W. , Meltzer, P. S. , George, D. L. , and Vogelstein, B. (1992) Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature 358:80–83.

    Article  Google Scholar 

  • Pai, E. F. , Krengel, U. , Petsko, G. A. , Goody, R. S. , Kabasch, W. , and Wittinghofer, A. (1990) Refined cyrstal structure of the triphosphate conformation of R-rasp21 at 1. 35 A resolution: implications for the mechanism of GTP hydrolysis. EMBO J.9, 8:2351–2359.

    Google Scholar 

  • Raycroft, L. , Wu, H. , and Lozano, G. (1990) Transcriptional activation by wild-type but not transforming mutants of the p53 anti-oncogene. Science 249:1049–1051.

    Article  Google Scholar 

  • Riccardi, V. M. (1991) Neurofibromatosis: past, present, and future. New England J. Med.324, 18:1283–1285.

    Article  Google Scholar 

  • Scheffner, M„ Werness, B. A., Huibregtse, J. M., Levine, A. J., and Howley, P. M. (1990) The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell63:1129–1136.

    Article  Google Scholar 

  • Sidransky, D. , Mikkelsen, T. , Schwechheimer, K. , Rosenblum, M. L. , Cavanee, W. , and Vogelstein, B. (1992) Clonal expansion of p53 mutant cells is associated with brain tumour progression. Nature 355:846–847.

    Article  Google Scholar 

  • Trahey, M. , Wong, G. , Halenbeck, R. , Rubinfeld, B. , Martin, G. A. , Ladner, M. , Long, C. M. , Crosier, W. J. , Watt, K. , Koths, K. , and McCormick, F. (1988) Molecular cloning of two types of GAP colementary DNA from human placenta. Science 242:1697–1700.

    Article  Google Scholar 

  • Vogelstein, B. and Kinzler, K. W. (1992) p53 function and dysfunction. Cell 70:523–526.

    Article  Google Scholar 

  • Von Hoff, D. D., McGill, J. R., Forseth, B. J., Davidson, K. K., Bradley, T. P., Van Devanter, D. R., and Wahl, G. M. (1992) Elimination of extrachromosomally amplified MYCgenes from human tumor cells reduces their tumorigenicity. Proc. Natl. Acad. Sci. USA 89:8165–8169.

    Article  Google Scholar 

  • Weintraub, S. J. , Prater, C. A. , and Dean, D. C (1992) Retinoblastoma protein switches the E2F site from positive to negative element. Nature 358:259–261.

    Article  Google Scholar 

  • WiesmĂĽller, L. and Wittinghofer, A. (1992) Expression of the GTPase activating domain of the neurofibromatosis type 2 (NF2) gene in escherichia coliand role of the conserved lysine residue. J. Biol. Chem.267, 15:10207–10210.

    Google Scholar 

  • Yin, Y. , Tainsky, M. A. , Bischoff, F. Z. , Strong, L. C. , and Wahl, G. M. (1992) Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles. Cell 70:937–948.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1993 Springer Basel AG

About this chapter

Cite this chapter

Dulbecco, R. (1993). The Impact of Molecular Genetics on Cancer Research. In: Cittadini, A., Baserga, R., Pinedo, H.M., Galeotti, T., Corda, D. (eds) Molecular Oncology and Clinical Applications. MCBU Molecular and Cell Biology Updates. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-5663-8_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-0348-5663-8_1

  • Publisher Name: Birkhäuser, Basel

  • Print ISBN: 978-3-0348-5665-2

  • Online ISBN: 978-3-0348-5663-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics