Principle investigator

PD Dr Jonathan Sleeman


Fon:
07247 82 6089

Fax:
07247 82 3354

eMail

Address:
Universität Karlsruhe
Postfach 3640
76021 Karlsruhe
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Animal tumor models for the evaluation of candidate gene function in tumor metastasis

Differential gene expression profiling in the first funding period of the NGFN identified genes that are up- or down-regulated during tumorigenesis and metastasis.

The challenge now is to use functional assays to identify those genes that play a role in metastasis. The complex process of tumor growth and metastasis can only be completely modelled in experimental animals. Using transplantable tumor cell line-based models, expression of candidate genes will be ectopically overexpressed by transfection or suppressed using RNAi in tissue cultured tumor cell lines.

The effect of the modified gene expression on tumor growth and metastasis will then be analysed by injecting the modified cells into syngeneic or immuno-suppressed animals as appropriate. Using genetically modified animal models, selected candidate genes will be either over-expressed using transgenesis, or expression of the gene will be ablated using targeted deletion. The modified mice will be bred onto backgrounds that develop tumors with a defined metastatic proclivity. The effect of the genetic modification of the germline on tumor growth and metastasis will then be assessed. These animal models will also be used for testing novel experimental anti-cancer therapies.