Table 2.
Experimental approach | Targeted tissues and cell types | Tumorigenic phenotype |
---|---|---|
Conditional endogenous expression of Lox-STOP-Lox- KrasG12D or Lox-STOP-Lox- NrasG12D cassette | Lung (intranasal administration of adenoviral Cre), pancreas (Pdx1-Cre or Ptf1a-Cre), colon (Fabp1-Cre) and the haematopoietic system (Mx1-Cre) | Lung adenocarcinoma, pancreatic intraepithelial neoplasia, colonic hyperplasia (KrasG12D), resistance to apoptosis (NrasG12D) and aggressive myeloproliferative disorder (KrasG12D)26, 27, 222–224 |
Endogenous expression of Lox-STOP-Lox-KrasG12V – IRES-β-galactosidase cassette | Whole-body (CMV-Cre) | Lung hyperplasia, adenocarcinoma and minor sarcoma lesions22 |
Transgenic expression of KrasG12V | Gastric and pancreatic epithelium (Krt19 promoter-driven KrasG12V) | Gastric cell hyperplasia225 |
Transgenic expression of HrasQ61L | Urothelium (Upk2 promoter-driven rabbit HrasQ61L) | Bladder tumorigenesis226 |
Inducible transgenic expression of KrasG12D | Basal layer of stratified epithelium (Krt5 promoter-driven tetracycline-responsive KrasG12D) | Neoplastic squamous epithelium: skin, forestomach and oesophagus227 |
Inducible transgenic expression of HrasG12V | Melanocytes (tyrosinase-driven tetracycline-responsive HrasG12V) | Melanoma78 |
Spontaneous chemical carcinogenesis | Skin (DMBA-TPA-induced mutagenesis of Hras) and lung (urethane-induced mutagenesis of Kras) | Skin papillomas and lung tumours 25, 228 |
Somatic oncogene transfer by RCAS-TVA gene delivery method | Brain (nestin-TVA-targeted expression of KrasG12D and Akt-myr) and pancreas (Lox-STOP-Lox-R26tva–LacZ/+-targeted expression of KrasG12D) | Glioblastoma and pancreatic intraepithelial neoplasia229, 230 |
Spontaneous recombination that results in expression of activated KrasG12D | Whole-body | Lung hyperplasia and carcinoma, thymic lymphoma and skin papilloma231 |
CMV, cytomegalovirus promoter; Fabp1, fatty acid binding protein 1, liver; IRES, internal ribosome entry site; Krt, keratin; Mx1, myxovirus resistance 1; myr, myristoylated; Pdx1, pancreatic and duodenal homeobox 1; Ptfa1, pancreas transcription factor 1, a-subunit; R26, ROSA 26; TPA, 12-O-tetradecanoyl-phorbol-13-acetate; Upk2, uroplakin 2.