NDLI: The role of MNK proteins and eIF4E phosphorylation in breast cancer cell proliferation and survival

Content Provider	PubMed Central
Author	Wheater, Matthew J. Johnson, Peter Wm Blaydes, Eremy P.
Copyright Year	2010
Abstract	eIF4E is overexpressed in many tumors, including a high proportion of breast cancers. eIF4E is an oncogene, and signaling pathways which promote eIF4E activity represent potential targets for therapeutic intervention in cancer. MNKs phosphorylate eIF4E on serine 209, a modification that can be required for eIF4E-dependent cell transformation. There is therefore a clear requirement to determine the role of MNKs in the proliferation and survival of cells from the major human tumors, such as breast cancer. Phosphorylated eIF4E protein was readily detectable in some breast tumor samples, but was below the limits of detection in others. Of six breast cancer cell lines representing the major subtypes of breast cancer, phosphorylated eIF4E was readily detectable in five of them, with MCF-7 cells displaying markedly lower levels. Long term colony forming assays demonstrated that all the five lines with high levels of phosphorylated eIF4E were highly sensitive to a MNK inhibitor. In short term assays, a range of responses was revealed. MCF-7 cells were insensitive in both assays. The anti-proliferative effects of the MNK inhibitor in breast cancer cells are primarily cytostatic, rather than cytotoxic, and are potentially due to the inhibition of cyclin D1 synthesis. Our data provide evidence that the sensitivity of breast cancer cells to MNK inhibition may correlate with baseline levels of eIF4E phosphorylation, and suggest that a proportion of breast cancers could be sensitive to inhibiting MNK kinase activity, and that the presence of phosphorylated eIF4E could provide a biomarker for the identification of responsive tumors.
Related Links	http://dx.doi.org/10.4161/cbt.10.7.12965
Ending Page	735
Page Count	8
Starting Page	728
File Format	PDF
ISSN	15384047
e-ISSN	15558576
Journal	Cancer Biology & Therapy
Issue Number	7
Volume Number	10
Language	English
Publisher	Landes Bioscience
Publisher Date	2010-10-01
Access Restriction	Open
Rights Holder	Landes Bioscience
Subject Keyword	Molecular Medicine Cancer Research Oncology Pharmacology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Pharmacology Molecular Medicine Oncology

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