Genome-wide inhibitory impact of the AMPK activator metformin on [kinesins, tubulins, histones, aurorasandpolo-like kinases] M-phase cell cycle genes in human breast cancer cells
Year: 2009
Type: article
Abstract: Prompted by the ever-growing scientific rationale for examining the antidiabetic drug metformin as a potential antitumor agent in breast cancer disease, we recently tested the hypothesis that the assessment of metformin-induced global changes in gene expression-as identified using 44 K (double density) Agilent's whole human genome arrays-could reveal gene-expression signatures that would allow proper selection of breast cancer patients who should be considered for metformin-based clinical trials. Using Database for Annotation, Visualization and Integrated Discovery bioinformatics (DAVID) resources we herein reveal that, at doses that lead to activation of the AMP-activated protein kinase (AMPK), metformin not only downregulates genes coding for ribosomal proteins (i.e., protein and macromolecule biosynthesis) but unexpectedly suppresses numerous mitosis-related gene families including kinesins, tubulins, histones, auroras and polo-like kinases. This is, to our knowledge, the first genome-scale evidence of a mitotic core component in the transcriptional response of human breast cancer cells to metformin. These findings further support a tight relationship between the activation status of AMPK and the chromosomal and cytoskeletal checkpoints of cell mitosis at the transcriptional level.
Source: Cell Cycle
DOI: 10.4161/cc.8.10.8406
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W2074782537