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View the Table of Contents for the July 15 issue of Cancer Research.
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Early exposure to xenoestrogens may be linked to breast cancer risk later in adult life, suggesting that epithelial progenitor cells are susceptible and may transmit these exposure injuries through epigenetic mechanisms to their differentiated progeny. Hsu and colleagues used progenitor-containing mammospheres to study the epigenetic effects of diethylstilbestrol (DES) exposure. MicroRNA-9-3 was found to be down-regulated with repressive chromatin marks at its locus, accompanied by an aberrant increase in DNA methylation of its promoter CpG island. Functional analyses suggest that miR-9-3 plays a role in the p53-related apoptotic pathway. Promoter hypermethylation of this microRNA may be a hallmark for early breast cancer development, with restoration of its expression an option for future treatment.
Sikkema et al. Page 5987 Sikkema and colleagues used flow-through peptide microarrays to generate kinome profiles to identify potential new targets when a priori aberrant kinase signaling activity is not necessarily known. Tyrosine kinase activity profiles were obtained from 29 pediatric brain tumors using the PamChip kinome profiling system. These profiles suggest the existence of a tumor-specific kinase activity profile including CDK2 and c-Met, confirming earlier reports on activation of these kinases. Furthermore, Src kinase was found to be highly phosphorylated and the Src kinase inhibitors PP1 and dasatinib induced substantial tumor death in pediatric brain tumor cell lines. These results demonstrate the usefulness of kinase activity profiling to identify new potential targets for treatment.
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