Keywords: 99mtc-Mibi, Apoptosis, Bcl-2, Breast Cancer, Prognostic Indicators, Apoptosis Inducing Factor, Methoxy Isobutyl Isonitrile Technetium Tc 99m, Protein Bcl 2, Staurosporine, Article, Cancer Cell, Controlled Study, Gene Overexpression, Genetic Transfection, Human, Human Cell, In Vivo Study, Molecular Cloning, Nucleotide Sequence, Protein Analysis, Protein Binding, Protein Stability, Breast Neoplasms, Cell Line, Tumor, Metabolic Clearance Rate, Proto-Oncogene Proteins C-Bcl-2, Radiopharmaceuticals, Recombinant Proteins, Technetium Tc 99m Sestamibi,
Affiliations: *** IBB - CNR ***
Ist. di Biostrutture e Bioimmagini, Sezione di Bioimmagini, Cons. Nazionale delle Ricerche (CNR), Napoli, Italy
Dipto. Sci. Biomorfol. Funzionali, Universita' Federico II, Napoli, Italy
References: Not available.
Bcl-2 overexpression prevents 99mTc-MIBI uptake in breast cancer cell lines
We have previously shown a correlation between 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 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.
Bcl-2 overexpression prevents 99mTc-MIBI uptake in breast cancer cell lines
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