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Anticancer genes act in a dominant fashion: when ectopically overexpressed they specifically destroy tumour cells without harming normal cells. This cell destruction can come in various modes such as apoptosis, mitotic catastrophe followed by apoptosis or necrosis, and autophagy. Anticancer genes have only recently emerged from studies on cancer cells. Anticancer genes comprise Apoptin, a gene encoded by the chicken anaemia virus genome which was the first anti-cancer gene isolated.〔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)〕 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.〔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).〕 The adenovirus E4orf4 is the second known viral protein with tumour-selective cell killing capabilities.〔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〕 HAMLET encodes the milk protein α-lactalbumin and is active against cancer cells only when complexed with oleic acid.〔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).〕 Mda-7 (also known as IL-24) encodes a secreted cytokine and belongs to the IL-10 gene family.〔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)〕 Noxa, is a BH3-only protein of the Bcl-2 family, has recently been discovered as a specific killer of breast cancer cells.〔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)〕 Parvovirus-H1 NS1 is another viral protein carrying tumour-selective apoptosis capabilities.〔Encyclopædia Britannica〕 ORCTL3, a cation transporter, was recently discovered as a novel anti-cancer gene.〔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).〕 Par-4 encodes a protein that features a leucine zipper and mediates many diverse signals for apoptosis at its endogenous expression level.〔El-Guendy, N. & Rangnekar, V.M. Apoptosis by Par-4 in cancer and neurodegenerative diseases. Exp Cell Res. 283, 51-66. (2003).〕 TRAIL (TNF related apoptosis-inducing ligand) is a member of the TNF family of apoptosis-inducing ligands 〔Sheridan, J.P. et al. Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science. 277, 818-21. (1997).〕 Some of these genes are in clinical development. TRAIL, Mda-7, HAMLET are the clinically most advanced anti-cancer genes. They are currently tested in clinical trials I and II, all other anti-cancer genes are in pre-clinical studies. == References == *Grimm, S., & Noteborn, M. (2010). Anticancer genes: inducers of tumour-specific cell death signalling Trends in Molecular Medicine, 16 (2), 88-96 References: 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Anticancer gene」の詳細全文を読む スポンサード リンク
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