Abstract
We have previously shown a correlation between the absence of technetium-99m methoxyisobutylisonitrile (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 intracellular protein levels and tested for 99mTc-MIBI uptake. All clones overexpressing Bcl-2 showed a dramatic reduction 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 basis for the development of an in vivo test to detect Bcl-2 overexpression in human tumours.
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Acknowledgements
This work was supported by Associazione Italiana Ricerca Cancro (AIRC) and Progetto FIRB-MIUR. We are grateful to Dr. G. Palumbo, Dipartimento di Biologia e Patologia, Cellulare e Molecolare, Universita’ “Federico II”, Napoli, Italy, for providing the pSFFV-hBcl-2 plasmid. Mr. Carmine Di Nuzzo, TSRM, provided excellent technical assistance for this work.
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Aloj, L., Zannetti, A., Caracó, C. et al. Bcl-2 overexpression prevents 99mTc-MIBI uptake in breast cancer cell lines. Eur J Nucl Med Mol Imaging 31, 521–527 (2004). https://doi.org/10.1007/s00259-003-1381-0
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DOI: https://doi.org/10.1007/s00259-003-1381-0