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.

Ellen T, Ke Q, Zhang P, Costa M.

Dept. of Environmental Medicine, Pharmacology and the NYU Cancer

Institute, New York University School of Medicine New York, N.Y.

10016.

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 upregulated 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 upregulated under hypoxic

conditions, and this condition is prevalent in solid tumors, its

regulation is somewhat complex, governed by hypoxia-inducible factor-

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

N-Myc, 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.