NF-kappaB as a critical link between inflammation and cancer.
NF-kappaB transcription factors have been suspected to be involved in cancer development since their discovery because of their kinship with the v-Rel oncogene product. Subsequent work led to identification of oncogenic mutations that result in NF-kappaB activation in lymphoid malignancies, but most of these mutations affect upstream components of NF-kappaB signaling pathways, rather than NF-kappaB family members themselves. NF-kappaB activation has also been observed in many solid tumors, but so far no oncogenic mutations responsible for NF-kappaB activation in carcinomas have been identified. In such cancers, NF-kappaB activation is a result of underlying inflammation or the consequence of formation of an inflammatory microenvironment during malignant progression. Most importantly, through its ability to up-regulate the expression of tumor promoting cytokines, such as IL-6 or TNF-alpha, and survival genes, such as Bcl-X(L), NF-kappaB provides a critical link between inflammation and cancer.
Karin
Michael
M
Department of Pharmacology and Pathology, Moores Cancer Canter, UCSD School of Medicine, La Jolla, California 92093-0723, USA. mkarin@ucsd.edu <mkarin@ucsd.edu>
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D003092:Colitis / Q000473:pathology; D005260:Female; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D009857:Oncogenes; D011471:Prostatic Neoplasms / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
D015850:Interleukin-6; D016328:NF-kappa B; D051020:bcl-X Protein