CMT 4D: NDRG1, a growth and cancer related gene: regulation of gene expression a

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NDRG1, a growth and cancer related gene: regulation of gene

expression and function in normal and disease states

P. Ellen, Qingdong Ke, Ping Zhang and Max Costa

Department of Environmental Medicine, Pharmacology and the NYU Cancer

Institute, New York University School of Medicine, New York, NY

10016, USA

N-myc downstream-regulated gene 1 (NDRG1) is an intracellular protein

that is induced under a wide variety of stress and cell growth-

regulatory conditions. NDRG1 is up-regulated by cell differentiation

signals in various cancer cell lines and suppresses tumor metastasis.

Despite its specific role in the molecular cause of Charcot–Marie–

Tooth type 4D disease, there has been more interest in the gene as a

marker of tumor progression and enhancer of cellular differentiation.

Because it is strongly up-regulated under hypoxic conditions, and

this condition is prevalent in solid tumors, its regulation is

somewhat complex, governed by hypoxia-inducible factor 1 alpha (HIF-

1)- and p53-dependent pathways, as well as its namesake,

neuroblastoma-derived myelocytomatosis, and probably many other

factors, at the transcriptional and translational levels, and through

mRNA stability. We survey the data for clues to the NDRG1 gene's

mechanism and for indications that the NDRG1 gene may be an efficient

diagnostic tool and therapy in many types of cancers