Anticancer gene

Anticancer genes are genes that, when ectopically overexpressed, specifically destroy tumour cells without harming normal cells.[1] This cell destruction can be due to a variety of mechanisms, such as apoptosis, mitotic catastrophe followed by apoptosis or necrosis, and autophagy. Anticancer genes emerged from studies on cancer cells in the late 1990s.[2]

Examples

The first anticancer gene to be isolated was Apoptin, a gene encoded by the chicken anaemia virus genome.[2] Brevinin-2R is a short anti-microbial peptide of only 25 amino acids, a so-called non-hemolytic defensin, isolated from the skin of the frog species Rana ridibunda.[3] The adenovirus E4orf4 is a viral protein with tumour-selective cell killing capabilities.[4] HAMLET encodes the milk protein α-lactalbumin and is active against cancer cells only when complexed with oleic acid.[5] Mda-7 (also known as IL-24) encodes a secreted cytokine and belongs to the IL-10 gene family.[6] Noxa, is a BH3-only protein of the Bcl-2 family, has recently been discovered as a specific killer of breast cancer cells.[7] Parvovirus-H1 NS1 is another viral protein carrying tumour-selective apoptosis capabilities.[8] ORCTL3, a cation transporter, was recently discovered as a novel anti-cancer gene.[9] Par-4 encodes a protein that features a leucine zipper and mediates many diverse signals for apoptosis at its endogenous expression level.[10] TRAIL (TNF related apoptosis-inducing ligand) is a member of the TNF family of apoptosis-inducing ligands [11]TP53 is another anti-cancer/anti-tumor gene (elephants have twenty copies of the TP53 gene).

Some of these genes are in clinical development. TRAIL, Mda-7, HAMLET are the clinically most advanced anticancer genes.

See also

References

  1. ↑ Grimm, Stefan; Noteborn, Mathieu. "Anticancer genes: inducers of tumour-specific cell death signalling". Trends in Molecular Medicine. 16 (2): 88–96. doi:10.1016/j.molmed.2009.12.002.
  2. 1 2 Danen-Van Oorschot, A.A. et al. Apoptin induces apoptosis in human transformed and malignant cells but not in normal cells. Proc. Natl. Acad. Sci. U S A 94, 5843-7 (1997)
  3. ↑ Ghavami, S. et al. Brevinin-2R(1) semi-selectively kills cancer cells by a distinct mechanism, which involves the lysosomal-mitochondrial death pathway. J Cell Mol Med. 12, 1005-22. (2008).
  4. ↑ Gingras, M.C., et al. (2002) Cytoplasmic death signal triggered by SRC-mediated phosphorylation of the adenovirus E4orf4 protein. Mol Cell Biol 22, 41-56
  5. ↑ Svensson, M., Hakansson, A., Mossberg, A.K., Linse, S. & Svanborg, C. Conversion of alpha-lactalbumin to a protein inducing apoptosis. Proc Natl Acad Sci U S A 97, 4221-6. (2000).
  6. ↑ Su, Z.Z. et al. The cancer growth suppressor gene mda-7 selectively induces apoptosis in human breast cancer cells and inhibits tumor growth in nude mice. Proc Natl Acad Sci U S A 95, 14400-5 (1998)
  7. ↑ Suzuki, S., Nakasato, M., Shibue, T., Koshima, I. & Taniguchi, T. Therapeutic potential of proapoptotic molecule Noxa in the selective elimination of tumor cells. Cancer Sci. 100, 759-69. Epub 2009 Mar 9. (2009)
  8. ↑ Encyclopædia Britannica
  9. ↑ Irshad, S., Mahul-Mellier, A.L., Kassouf, N., Lemarie, A. & Grimm, S. Isolation of ORCTL3 in a novel genetic screen for tumor-specific apoptosis inducers. Cell Death Differ 16, 890-898 (2009).
  10. ↑ El-Guendy, N. & Rangnekar, V.M. Apoptosis by Par-4 in cancer and neurodegenerative diseases. Exp Cell Res. 283, 51-66. (2003).
  11. ↑ Sheridan, J.P. et al. Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science. 277, 818-21. (1997).
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.