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tumorigenesis

Sunday 13 July 2003

carcinogenesis, oncogenesis, tumoral transformation ; tumorigenicity

Definition: Tumorigenesis is a collection of complex genetic diseases characterized by multiple defects in the homeostatic mechanisms that regulate cell growth, proliferation and differentiation.

Cancer is caused by uncontrolled proliferation and the inappropriate survival of damaged cells, which results in tumour formation. Cells have developed several safeguards to ensure that cell division, differentiation and death occur correctly and in a coordinated fashion, both during development and in the adult body.

Many regulatory factors switch on or off genes that direct cellular proliferation and differentiation. Damage to these genes, which are referred to as tumour-suppressor genes and oncogenes, is selected for in cancer.

Most tumour-suppressor genes and oncogenes are first transcribed from DNA into RNA, and are then translated into protein to exert their effects. Recent evidence indicates that small non-protein-coding RNA molecules, called microRNAs (miRNAs), might also function as tumour suppressors and oncogenes.

Mechanisms (Examples)

 activation of oncogenes

 sequential inactivation of tumor suppressor genes
 tumoral pathways
 tumoral epigenetics
 inflammatory-mediated tumorigenesis

Localization

 digestive tumorigenesis
 endocrine tumorigenesis

 gliomagenesis (tumorigenesis of glioma )
 mammary tumorigenesis

See also

 multistep tumorigenesis

References

 Bardelli A, Velculescu VE. Mutational analysis of gene families in human cancer. Curr Opin Genet Dev. 2005 Feb;15(1):5-12. PMID: 15661527

 Boehm JS, Hahn WC. Understanding transformation: progress and gaps. Curr Opin Genet Dev. 2005 Feb;15(1):13-7. PMID: 15661528

 Gregory RI, Shiekhattar R. Chromatin modifiers and carcinogenesis. Trends Cell Biol. 2004 Dec;14(12):695-702. PMID: 15564046

 Zhao JJ, Roberts TM, Hahn WC. Functional genetics and experimental models of human cancer. Trends Mol Med. 2004 Jul;10(7):344-50. PMID: 15242683

 Felsher DW. Reversibility of oncogene-induced cancer. Curr Opin Genet Dev. 2004 Feb;14(1):37-42. PMID: 15108803

 Sieber OM, Heinimann K, Tomlinson IP. Genomic instability—the engine of tumorigenesis? Nat Rev Cancer. 2003 Sep;3(9):701-8. PMID: 12951589

 Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 2003 Jun;3(6):401-10. PMID: 12778130

 Hahn WC, Weinberg RA. Rules for making human tumor cells.
N Engl J Med. 2002 Nov 14;347(20):1593-603. PMID: 12432047

 Manson MM. Cancer prevention — the potential for diet to modulate molecular signalling. Trends Mol Med. 2003 Jan;9(1):11-8. PMID: 12524205

 Wu X, Pandolfi PP. Mouse models for multistep tumorigenesis. Trends Cell Biol. 2001 Nov;11(11):S2-9. PMID: 11684435

 Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000 Jan 7;100(1):57-70. PMID: 10647931

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