Abstract |
Nm23-H1 significantly reduces metastasis without effects on primary tumor size and was the first discovered metastasis suppressor gene. At least three mechanisms are thought to contribute to the metastasis-suppressive effect of Nm23-H1: (a) its histidine kinase activity toward ATP-citrate lyase, aldolase C, and the kinase suppressor of ras, with the last inactivating mitogen-activated protein kinase signaling; (b) binding proteins that titer out "free" Nm23-H1 and inhibit its ability to suppress metastasis; and (c) altered gene expression downstream of Nm23-H1, particularly an inverse association with the lysophosphatidic acid receptor endothelial differentiation gene-28 (EDG2). Most metastasis suppressor genes, including Nm23-H1, affect metastatic colonization, which is the outgrowth of tumor cells in distant locations; therefore, they are of high translational interest. A phase II trial is ongoing to test the hypothesis that a compound, high-dose medroxyprogesterone acetate (MPA), used as an unconventional gluocorticoid, will stimulate breast cancer cells to reexpress Nm23-H1 and limit subsequent metastatic colonization.
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Authors | Patricia S Steeg, Christine E Horak, Kathy D Miller |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 14
Issue 16
Pg. 5006-12
(Aug 15 2008)
ISSN: 1078-0432 [Print] United States |
PMID | 18698018
(Publication Type: Journal Article, Review)
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Chemical References |
- Antineoplastic Agents
- NM23 Nucleoside Diphosphate Kinases
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Clinical Trials, Phase II as Topic
- Humans
- NM23 Nucleoside Diphosphate Kinases
(drug effects, physiology)
- Neoplasm Invasiveness
(genetics)
- Neoplasms
(drug therapy, enzymology)
- Signal Transduction
(drug effects, physiology)
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