Increased radioiodine accumulation in thyroid and breast carcinoma by tanespimycin

Objectives Tanespimycin, an inhibitor of heat shock protein 90 (HPS 90), has been tried to increase radioiodine accumulation in thyroid carcinoma. We investigated the effect of tanespimycin on accumulation and excretion of radioiodines in thyroid and breast carcinoma cells.

Methods In FRTL-5 (rat thyroid follicular cells), CMV-hNIS transfected ARO (human thyroid anaplastic cancer) and MDA-MB-231 (human breast carcinoma) cells, tanespimyin (1 uM) was treated for 48 h and 125I uptake and efflux were assessed. RT-PCR and Western blotting were performed to monitor the expression of HER1, HER2, HSP40, HSP70, HSP90, NIS and PDS. In addition, 125I accumulation and efflux rate were measured in HSP40, HSP70, HSP90 and PDS over expressed cells.

Results In tanespimycin treated FRTL-5, ARO and MDA-MB-231 cells, 125I accumulation was increased about 2.5 folds, although NIS mRNA level was slightly decreased. The efflux rate of 125I from cells was notably reduced by tanespimycin. We monitored the significant increase of HSP40, HSP70 and HSP90 expression after tanespimycin treatment; however, over expression of HSPs did not alter the accumulation of 125I. The targets of tanespimycin, the HSP90 client proteins, HER1 and HER2 were meaningfully decreased.

Conclusions Even though tanespimycin is famous as a HSP90 inhibitor and increases the protein levels of HSPs, our results indicate that prolonged retention of 125I was not directly related to the increased amount of HSPs. However, we could demonstrate that Tanespimycin increased 125I accumulation in thyroid and breast carcinoma by reducing the efflux rate of 125I