| title: | Modulation of the Hedgehog signalling activity in vivo: its potential in cancer therapy |
|---|---|
| reg no: | ETF6139 |
| project type: | Estonian Science Foundation research grant |
| status: | accepted |
| institution: | Institute of Chemical Physics and Biophysics |
| head of project: | Illar Pata |
| duration: | 01.01.2005 - 31.12.2008 |
| description: | Hedgehog (Hh) signalling pathway is essential in controlling patterning, growth and cell proliferation in several organ systems, in an embryo and the adult. Hh activity is therefore tightly regulated by inhibitors, such as the Hh receptor Patched (Ptch). Inappropriate activation or maintenance of Hh signalling often results in tumorigenesis (medulloblastomas and basal cell carcinomas). This project investigates the possibility to modulate Hh signalling by downregulating the expression of activators of the Hh pathway, Gli factors, and hence restrain cancer formation. We will use mice heterozygous for Ptch that develop frequent tumors as a model system. We take advantage of the RNA interference knockdown technology combined with Cre-lox system to identify the key targets in Hh pathway, capable of inhibiting tumor growth. As delivery system, we focus to the use of lentiviral vectors that simplify constructing transgenic mice and thus make these aims realistic. We expect that downregulation of Gli factors individually or in combination will rescue Ptch+/- phenotype. This study will provide novel insight into the role and regulation of the Hh signalling pathway. Lentiviral vectors are also potential therapeutic vehicles, and results of this study could have direct clinical applications in treatment of cancer. |
| project group | ||||
|---|---|---|---|---|
| no | name | institution | position | |
| 1. | Alla Maloverjan | Tallinn Technical University | Researcher | |
| 2. | Illar Pata | Institute of Chemical Physics and Biophysics | assistant scientist | |
| 3. | Richard Tamme | Institute of Chemical Physics and Biophysics | postdoctoral research fellow | |
| 4. | Robert Tsanev | KBFI/TTÜ | NICBP research scientist , Tallinn Technical Unive | |