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

BMC Cancer
Maria Teresa ValentiVincenzo Lo Cascio

Abstract

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

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Citations

Aug 21, 2012·Journal of Bone and Mineral Metabolism·Mirko ZanattaLuca Dalle Carbonare
Aug 23, 2012·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Chunmei GuoMing-Zhong Sun
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Oct 16, 2019·Experimental and Therapeutic Medicine·Benjaporn BuranratVeerapol Kukongviriyapan
Mar 19, 2021·Genetic Testing and Molecular Biomarkers·Bojana UzelacGordana Supic
Nov 12, 2009·European Journal of Pharmacology·Yoshiki TatsudaKazuyuki Hirano

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Methods Mentioned

BETA
electrophoresis
PCR

Software Mentioned

Statgraphics Plus

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