Reversible tumorigenesis in mice by conditional expression of the HER2/c-erbB2 receptor tyrosine kinase.
In the present study we describe the reversible transformation of NIH3T3 fibroblasts by overexpression of the HER2/c-erbB2 receptor tyrosine kinase. Cell lines expressing HER2 under control of a tetracycline-responsive promoter were isolated. Induction of HER2 expression resulted in cellular transformation in vitro as depicted by growth in soft agar and focus formation in tissue culture. Subsequent treatment of these cells with the effector anhydrotetracyline switched-off HER2 expression and induced morphological and functional changes characteristic for non-transformed cells. Subcutaneous transplantation of cells in nude mice resulted in the formation of solid tumors. Interestingly tumor formation was completely suppressed by treatment of the animals with anhydrotetracyline. Our findings indicate that overexpression of HER2 induces the transformed phenotype of NIH3T3 cells and is required for tumor formation and progression in nude mice. By linking the expression of the marker gene secreted placental alkaline phosphatase to the expression of HER2, a sensitive monitoring of tumor development in nude mice was feasible.
Baasner
S
S
Department of Cancer Research, ASTA Medica AG, Frankfurt/Main, Germany.
von Melchner
H
H
Klenner
T
T
Hilgard
P
P
Beckers
T
T
D016475:3T3 Cells; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy; D010641:Phenotype; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D013752:Tetracycline / Q000494:pharmacology; D013754:Tetracyclines / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics; D014158:Transcription, Genetic; D014183:Transplantation, Heterologous
D000469:Alkaline Phosphatase; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D012097:Repressor Proteins; D013752:Tetracycline; D013754:Tetracyclines; D015534:Trans-Activators; C034811:tetracycline resistance-encoding transposon repressor protein; C016229:4-epianhydrotetracycline