DNA methylation and breast cancer.
DNA methylation and chromatin structure patterns are tightly linked components of the epigenome, which regulate gene expression programming. Two contradictory changes in DNA methylation patterns are observed in breast cancer; regional hypermethylation of specific genes and global hypomethylation. It is proposed here that independent mechanisms are responsible for these alterations in DNA methylation patterns and that these alterations deregulate two different processes in breast cancer. Regional hypermethylation is brought about by specific regional changes in chromatin structure, whereas global demethylation is caused by a general increase in demethylation activity. Hypermethylation silences growth regulatory genes resulting in uncontrolled growth whereas hypomethylation leads to activation of genes required for metastasis. DNA methylation inhibitors activate silenced tumor suppressor genes resulting in arrest of tumor growth and are now being tested as candidate anticancer drugs. Demethylation inhibitors are proposed here to be potential novel candidate antimetastatic agents, which would bring about methylation and silencing of metastatic genes. Future therapeutic application of either methylation or demethylation inhibitors in cancer therapy would require understanding of the relative role of these processes in the evolution of cancer.
Szyf
Moshe
M
Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osier Promenade, Montreal, Canada PQ H3G 1Y6. moshe.szyf@mcgill.ca
Pakneshan
Pouya
P
Rabbani
Shafaat A
SA
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry / Q000235:genetics; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans
D002843:Chromatin