Table 1.
A selection of representative studies illustrating the diverse applications of Tet-technology in functional cancer research.
| Model System | Regulatory Element(s) | Description of the Study | Reference |
|---|---|---|---|
| Cells in vitro and subcutaneous xenografts | tTA | Inducible over-expression of membrane-type-1 matrix metalloproteinase (MT1-MMP) in non-malignant MDCK epithelial cells is by itself sufficient to drive formation of invasive tumors. | (Soulie et al. 2005) |
| Cells in vitro and subcutaneous xenografts | tTA | Induction of fibroblast growth factor–2 (FGF-2) expression in human endometrial adenocarcinoma cells deeply affects the initial tumor growth and neovascularization but does not affect the progression of large tumors. | (Giavazzi et al. 2001) |
| Cells in vitro and orthotopic xenografts | tTA | Demonstration that actinin-4 actively increases cell motility and promotes lymph node metastasis of colorectal cancer. The Tet-off system was used to express actinin-4 in DLD-1 colorectal cancer cells. | (Honda et al. 2005) |
| Cells in vitro and subcutaneous xenografts | rtTA | This study shows that inducible expression of Bcl-Xs in human melanoma cells triggers apoptosis in vitro and delays growth of tumor xenografts in vivo. | (Hossini et al. 2003) |
| Cells in vitro and orthotopic xenografts | rtTA | Using the Tet-on system in malignant astrocytoma cells, it was shown that p125FAK can promote tumor cell proliferation in vivo and that it was not due to less apoptosis. | (Wang et al. 2000) |
| Cells in vitro and subcutaneous xenografts | tTA rtTA |
Antisense mRNA against mtCLIC/CLIC4 chloride channel protein expressed using Tet-off and Tet-on systems inhibited tumor growth and induced tumor apoptosis in human osteosarcoma cells. | (Suh et al. 2005) |
| Cells in vitro | rtTA2S-M2 tTS |
Inducible expression of GD3 ganglioside in glioblastoma cells was associated with apoptosis occurring via caspase-8 activation. | (Saqr et al. 2006) |
| Transgenic mice* | tTA | Sustained expression of the MYC transgene in hematopoietic cells resulted in the formation of malignant T cell lymphomas and acute myeloid leukemias. The subsequent inactivation of the transgene caused regression of established tumors. | (Felsher and Bishop, 1999) |
| Transgenic mice* | tTA | Inducible expression of P210 BCR-ABL in stem and progenitor cells of murine bone marrow resulted in splenomegaly, myeloid bone marrow hyperplasia and extrameddulary myeloid cell infiltration of multiple organs. This recapitulates many characteristics of human chronic myeloid leukemia (CML). | (Koschmieder et al. 2005) |
| Transgenic mice* | rtTA | Demonstration that melanoma genesis and maintenance are strictly dependent upon expression of V12 H-Ras in a Dox-inducible V12 H-Ras mouse melanoma model null for the tumor suppressor INK4a. | (Chin et al. 1999) |
| Transgenic mice* | rtTA | Inducible expression of activated receptor tyrosine kinase HER2/Neu in the mammary epithelium of transgenic mice resulted in development of multiple invasive mammary carcinomas that regressed following transgene deinduction demonstrating that Neu-initiated tumorigenesis is reversible. However the animals bearing regressed tumors ultimately developed Neu-independent recurrent tumors. | (Moody et al. 2002) |
| Cells in vitro | TetR tTA | Using breast cancer cell lines engineered to inducibly express or inducibly suppress expression of the Fra-1 gene the authors demonstrate a positive association between Fra-1 levels and cell proliferation, motility and invasiveness. | (Belguise et al. 2005) |
| Cells in vitro and orthotopic xenografts | TetR | Pol III promoter driven conditional expression of shRNA against PI-3 kinase subunits p110α and p110β showed a significant reduction in the formation of metastases following p110β but not p110α downregulation in prostate cancer cells. | (Czauderna et al. 2003) |
| Subcutaneous xenografts | TetR | Inducible downregulation of HIF-1α resulted in transcient tumor stasis and tumor regression. Inhibiting HIF-1α in early stage tumors was more efficacious than inhibiting HIF-1α in more established tumors. | (Li et al. 2005) |
| Subcutaneous xenografts | TetR | Inducible silencing of the candidate tumor suppressor KILLER/DR5 in colon cancer cell lines resulted in accelerated growth of tumor xenografts and conferred resistance to the chemotherapeutic agent 5-fluorouracil | (Wang and El-Deiry, 2004) |
| 3D cell culture in vitro and orthotopic xenografts | TetR | This study shows that a protein kinase C related molecule PKN3 is required for invasive prostate cell growth. | (Leenders et al. 2004) |
| Cells in vitro and subcutaneous xenografts | tTA rtTA |
Inducible RNA interference using microRNA-based shRNA expressed from the Pol II promoter. Tumors induced by Trp53 suppression and cooperating oncogenes regressed upon re-expression of Trp53. | (Dickins et al. 2005) |
*
Several additional examples of the use of Tet-transgenic mice in cancer research can be found in the recent paper by (Felsher, 2004).