Amino-bisphosphonates decrease hTERT gene expression in breast cancer in vitro.

BACKGROUND AND AIMS: Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of telomerase. hTERT expression and telomerase activity are elevated in most human tumors. Bisphosphonates play an important role in the management of tumors with the secondary involvement of bone. METHODS: We investigated the effect on hTERT gene expression of clodronate, alendronate, and pamidronate (from 10(-6) M to 10(-5) M) on MCF-7 and T47D human breast cancer cells, using real time RTPCR. RESULTS: At 10(-5) M, amino-bisphosphonates (alendronate and pamidronate) inhibited breast cancer cell viability and induced a significant decrease in hTERT gene expression with respect to controls (82% and 71% in MCF-7 cells; 74% and 60% in T47D, p<0.0001). No effect was observed with clodronate. CONCLUSIONS: Amino-bisphosphonates down-regulate hTERT gene expression. The role of hTERT is a new finding, which gives an alternative explanation for the direct effect of bisphosphonates on tumor cells.