INHIBITION OF TUMOR-GROWTH BY A DOMINANT-NEGATIVE MUTANT OF THE INSULIN-LIKE-GROWTH-FACTOR-I RECEPTOR WITH A BYSTANDER EFFECT

The insulin-like growth factor I receptor is known to play a major rol e in transformation and apoptosis. The dominant negative mutant of the insulin-like growth factor I receptor, designated 486/STOP, causes ma ssive apoptosis of tumor cells and inhibition of tumor growth and meta stases. We now show that: (a) the stable expression of 486/STOP inhibi ts transformation (colony formation in soft agar) and/or tumor growth in nude mice of five different types of human tumor cell lines; and (b ) more importantly, it has a bystander effect, inhibiting the growth o f wild-type tumor cells when cells expressing 486/STOP are coinjected with wild-type tumor cells. These findings suggest that it is not nece ssary to infect all tumor cells with 486/STOP to inhibit tumor growth, and they also open the possibility of using the product of 486/STOP d irectly against tumor cells.