Lung Cancer |
Lentiviral-mediated Ikbkb deletion in a lung model of adenocarcinoma expressing KrasG12D and shp53. | Attenuated tumor proliferation and significantly prolonged mouse survival. | Down-regulation of the NF-κB target TIMP-1 and ERK pathway; reduced cell proliferation. | [47] |
Melanoma |
Dox-induced Ikbkb deletion in melanocytes expressing HRasG12V in INK4A/ARF-null background. | Inhibition of melanoma tumor development. | p53-dependent cell cycle arrest and apoptosis. | [51] |
Ikbkb deletion in myeloid cells in a mouse model injected with BRAFV600E /PTEN−/− melanoma cells. | Growth of cutaneous and lung melanoma tumors. | Myeloid IKKβ promotes antitumor immunity by modulating the chemokine CCL11 and the innate immune response. | [52] |
Pancreatic Cancer |
Cre-mediated Ikbkb deletion in a model expressing KrasG12D in the pancreas. | Reduced progression of pancreatic neoplasia. | Downregulation of inflammatory cytokines and chemokines; downregulation of Notch signaling; PPARG inhibition. | [53] |
Cre-mediated Ikbkb deletion in a model expressing KrasG12D in the pancreas (also in INK4A/ARF null background). | Reduced formation of pancreatic neoplasia and of pancreatic ductal adenocarcinomas. | Inhibition of inflammation and NFκB activation. | [54] |
Liver Cancer |
Cre-mediated Ikbkb deletion in hepatocytes. | Enhanced DEN-induced hepatocarcinogenesis. | Increased cell death and compensatory proliferation mediated by increased ROS production and JNK1 activation. | [55,56] |
Ikbkb deletion in initiated hepatocytes transplanted onto mice expressing PLAU in hepatocytes. | Enhanced formation of hepatocellular carcinomas. | Enhanced ROS production and STAT3 activation. | [57] |
Cre-mediated Ikbkb deletion in hepatocytes and hematopoietic-derived Kupffer cells. | Decreased DEN-induced hepatocarcinogenesis and reduced hepatocyte regeneration. | Diminished induction of hepatic mitogens (IL-6, TNFα and HGF). | [55] |
Intestinal Cancer |
Cre-mediated Ikbkb deletion in intestinal epithelial cells. | Decreased tumor incidence in a colitis-associated cancer model. | Enhanced p53-independent apoptosis and defective Bcl-xL induction in tumor promotion. | [58] |
Cre-mediated Ikbkb deletion in myeloid cells. | Decreased tumor incidence and size in a colitis-associated cancer model. | Reduced expression of proinflammatory mediators without effect on apoptosis. | [58] |
Expression of constitutively active IKKβ in intestinal epithelial cells. | Spontaneous tumorigenesis and enhanced carcinogenesis induced by APC mutation or chemical treatments. | Activation of Wnt signaling and production of a pro-inflammatory intestinal microenvironment. | [59] |
Ikbkb deletion in mesenchymal cells mediated by a constitutive ColVI-Cre transgene. | Protection against inflammation-induced intestinal carcinogenesis. | IKKβ in mecenchimal cell causes an increase in IL-6 production and STAT3 activation. | [60] |
Ikbkb deletion in mesenchymal cells mediated by an inducible Col1a2Cre-ER transgene. | Stimulated intestinal proliferation, increased angiogenesis and promotion of colonic tumor growth. | IKKβ down-regulates TGFβ signaling and HGF secretion. | [61] |
Non-Melanoma Skin Cancer |
Constitutive K14-Cre mediated Ikbkb deletion in epidermal keratinocytes. | Severe inflammatory skin disease leading to death before postnatal day 10. | Unbalanced immune skin homeostasis, mediated by TNFα. | [62] |
Inducible K14-CreER mediated Ikbkb deletion in epidermal keratinocytes. | Skin inflammation, hair follicle disruption and epidermal pseudoepitheliomatous hyperplasia but not tumor formation. | Ikbkb deletion leads to STAT3 and ERK1/2 activation. | [63] |
Unexpected Ikbkb deletion in skin keratinocytes mediated by a GFAP-Cre transgene. | Skin hyperplasia, inflammation and development of SCCs in part of the mice. | Increased TNFα expression in lesions. | [64] |
Unexpected Ikbkb deletion in skin keratinocytes mediated by a OX40-Cre transgene. | Hyperplasia and inflammatory skin lesions. | Increased TNFα expression in lesions and T lymphocyte activation. | [65] |
IKKβ overexpression in epidermal keratinocytes by a K5-IKKβ transgene. | Resistance to tumor development in chemically-induced NMSC models. | Tumor-protective function of IKKβ is mediated by tumor suppressor proteins p16 and/or p19. | [66] |
Oral and Esophageal Cancer |
IKKβ overexpression in oral epithelial keratinocytes by a K5-IKKβ transgene. | Spontaneous oral tumoral lesions and increased malignancy after oral chemical carcinogenesis. | Enhanced oral inflammation with infiltration of granulocytes, macrophages and B lymphocytes. | [67] |
Expression of constitutively active IKKβ in esophageal epithelia. | Esophagitis and increased angiogenesis in esophageal stroma. | Increased production and secretion of GM-CSF and TNF. | [68] |