Amino-bisphosphonates decrease hTERT gene expression in breast cancer in vitro.
OBJECTIVE
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.
Dalle Carbonare
Luca
L
Department of Biomedical and Surgical Sciences, Medicina Interna D, University of Verona, Verona, Italy. luca.dallecarbonare@univr.it
Valenti
Maria T
MT
Bertoldo
Francesco
F
Fracalossi
Arianna
A
Balducci
Elena
E
Azzarello
Giuseppe
G
Vinante
Orazio
O
Lo Cascio
Vincenzo
V
D019386:Alendronate / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004002:Clodronic Acid / Q000494:pharmacology*; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D000077268:Pamidronate; D019098:Telomerase / Q000235:genetics*
D004164:Diphosphonates; D004002:Clodronic Acid; C509186:TERT protein, human; D019098:Telomerase; D000077268:Pamidronate; D019386:Alendronate