Bcl-2 overexpression prevents 99mTc-MIBI uptake in breast cancer cell lines

We have previously shown a correlation be- tween the absence of technetium-99m methoxyisobutyl- isonitrile (99mTc-MIBI) uptake and overexpression of the anti-apoptotic protein Bcl-2 in human breast carcinoma. To establish a direct cause-effect relationship between Bcl-2 overexpression and reduced 99mTc-MIBI uptake, MCF-7 and T47D breast cancer cell lines were stably transfected with the human Bcl-2 gene to increase intra- cellular protein levels and tested for 99mTc-MIBI uptake. All clones overexpressing Bcl-2 showed a dramatic re- duction of 99mTc-MIBI uptake as compared with mock transfected control cells. Tracer uptake was promptly and partially restored by induction of apoptosis with staurosporine treatment. After 4.5 h of staurosporine treatment, a tenfold increase in 99mTc-MIBI uptake was observed in treated as compared with untreated Bcl-2 overexpressing cells. Our findings provide a rational ba- sis for the development of an in vivo test to detect Bcl-2 overexpression in human tumours.