Tumor Suppressor Genes
The isolation of the first human tumor suppressor gene in 1986 fueled an immediate interest in gene replacement therapy as a novel treatment modality for human cancers (Friend et al. 1986) . The functional groundwork for the efficacy of this avenue of approach came from studies on the genetics of cancer using somatic cell genetics. The first report, in 1969, of the suppression of malignancy in hybrid cells between tumorigenic and nontumorigenic mouse cells provided evidence that normal cells possess genetic information capable of reversing many transformed features of tumor cells (Harris et al. 1969) . Since that initial study, many investigators have shown that introduction of normal genetic information into human cancer cells can cause suppression of cell growth in vitro and in vivo (Stanbridge 1992). Thus, the challenge facing scientists interested in the development of cancer gene therapies lies in the optimal delivery of potent tumor suppressor genes into tumor cells in vivo which can render them quiescent or prime them for destruction by other methods. This chapter will cover the identification of known tumor suppressor genes as well as the strategies to isolate novel tumor suppressor genes with different mechanisms of action.
KeywordsEstrogen Leukemia Polypeptide Beach Progesterone
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- Fukudome K, Fururse M, Imai T et al (1992) Identification of membrane antigen C33 recognized by monoclonal antibodies inhibitory to human T-cell leukemia virus type 1 (HTLV-l)-induced syncytium formation: altered gly-cosylation of C33 antigen in HTLV-1-positive T cells. J Virol 66:1394–1401PubMedGoogle Scholar
- Giard DJ, Aaronson SA, Todaro GJ et al (1974) In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors. J Natl Cancer Inst 51:1417–1423Google Scholar
- Imai T, Fukudome K, Tagai S et al (1992) C33 antigen recognized by monoclonal antibodies inhibitory to human T cell leukemia virus type 1-induced syncytium formation is a member of a new family of transmembrane proteins including CD9, CD37, CD53, and CD63. J Immunol 149:2879–2886PubMedGoogle Scholar
- Misra BC, Srivatsan ES (1989) Localization of HeLa cell tumor-suppressor gene to the long arm of chromosome 11. Am J Human Genet 45:565–577Google Scholar
- Muktar H, Bickers DR (1993) Environmental skin cancer: mechanisms, models and human cancer. Cancer Res 53:3439–3442Google Scholar
- Weissman BE (1990) Genetic behaviour of tumor genicity in human cancer. In: Cavenee W, Ponder B, Solomon E (eds) Cancer surveys-genetics and cancer, vol 9. Oxford University Press, Oxford, pp 475–485Google Scholar
- Weissman BE, Conway K (1995) Genetic aspects of tumor suppressor genes. Adv Genome Biol 3A: 137–156Google Scholar
- Weissman BE, Stanbridge EJ (1983) Complementation of the tumorigenic phenotype in human cell hybrids. J Natl Cancer Inst 70:666–672Google Scholar
- Winquist R, Mannerma A, Alvaikko M et al (1993) Refinement of regional loss of heterozygosity for chromosome 11pl5.5 in human breast tumors. Cancer Res 53:4486–4488Google Scholar