Bcl-2 overexpression prevents 99mTc-MIBI uptake in breast cancer cell lines.
We have previously shown a correlation between the absence of technetium-99m methoxyisobutylisonitrile ((99m)Tc-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 (99m)Tc-MIBI uptake, MCF-7 and T47D breast cancer cell lines were stably transfected with the human Bcl-2 gene to increase intracellular protein levels and tested for (99m)Tc-MIBI uptake. All clones overexpressing Bcl-2 showed a dramatic reduction of (99m)Tc-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 (99m)Tc-MIBI uptake was observed in treated as compared with untreated Bcl-2 overexpressing cells. Our findings provide a rational basis for the development of an in vivo test to detect Bcl-2 overexpression in human tumours.
Aloj
Luigi
L
Istituto di Biostrutture e Bioimmagini, Sezione di Bioimmagini, Consiglio Nazionale delle Ricerche (CNR), Via S. Pansini 5, Edificio 10, 80131 Napoli, Italy.
Zannetti
Antonella
A
Caracó
Corradina
C
Del Vecchio
Silvana
S
Salvatore
Marco
M
D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003001:Cloning, Molecular / Q000379:methods; D006801:Humans; D008657:Metabolic Clearance Rate; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011994:Recombinant Proteins / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology*; D017256:Technetium Tc 99m Sestamibi / Q000493:pharmacokinetics*; D014162:Transfection
D019253:Proto-Oncogene Proteins c-bcl-2; D019275:Radiopharmaceuticals; D011994:Recombinant Proteins; D017256:Technetium Tc 99m Sestamibi; D019311:Staurosporine