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Open Access Highly Accessed Research article

The effect of bisphosphonates on gene expression: GAPDH as a housekeeping or a new target gene?

Maria Teresa Valenti1, Francesco Bertoldo1, Luca Dalle Carbonare1*, Giuseppe Azzarello2, Sonia Zenari1, Mirko Zanatta1, Elena Balducci2, Orazio Vinante2 and Vincenzo Lo Cascio1

Author Affiliations

1 Medicina Interna D, Department of Biomedical and Surgical Sciences, University of Verona, Italy

2 Department of Oncology and Hematologic Oncology - Noale Hospital, Italy

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BMC Cancer 2006, 6:49  doi:10.1186/1471-2407-6-49

Published: 3 March 2006

Abstract

Background

RT-PCR has been widely used for the analysis of gene expression in many systems, including tumor samples. GAPDH (Glyceraldehyde-3-phosphate dehydrogenase) has been frequently considered as a constitutive housekeeping gene and used to normalize changes in specific gene expression. However, GAPDH has been shown to be up-regulated in many cancers and down-regulated by chemotherapic drugs. Bisphosphonates, potent inhibitors of bone resorption, have recently shown a direct and indirect antitumor effect in vitro and in animal models. They exert their effects mainly by inhibiting the mevalonate pathway but also by modulating the expression of many genes not only in osteoclasts but also in cancer cells.

Methods

We evaluated GAPDH gene expression by real time RT PCR in breast (MCF-7 and T47D) and prostate (PC3 and DU-145) cancer cell lines treated with amino and non-amino bisphosphonates.

Results

Our results showed that amino-bisphosphonates significantly decrease in a dose-dependent manner the expression of GAPDH gene.

Conclusion

Therefore, GAPDH is inaccurate to normalize mRNA levels in studies investigating the effect of bisphosphonates on gene expression and it should be avoided. On the other hand, this gene could be considered a potential target to observe the effects of bisphosphonates on cancer cells.