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Regulation of ornithine decarboxylase during oncogenic transformation: mechanisms and therapeutic potential

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Summary.

The activity of ornithine decarboxylase (ODC1), the first enzyme in polyamine biosynthesis, is induced during carcinogenesis by a variety of oncogenic stimuli. Intracellular levels of ODC and the polyamines are tightly controlled during normal cell growth, and regulation occurs at the levels of transcription, translation and protein degradation. Several known proto-oncogenic pathways appear to control ODC transcription and translation, and dysregulation of pathways downstream of ras and myc result in the constitutive elevation of ODC activity that occurs with oncogenesis. Inhibition of ODC activity reverts the transformation of cells in vitro and reduces tumor growth in several animal models, suggesting high levels of ODC are necessary for the maintenance of the transformed phenotype. The ODC irreversible inactivator DFMO has proven to be not only a valuable tool in the study of ODC in cancer, but also shows promise as a chemopreventive and chemotherapeutic agent in certain types of malignancies.

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Abbreviations

AdoMetDC:

S-adenosylmethionine decarboxylase

AZ:

antizyme

BCNU:

1,3-bis(2-chloroethyl)-1-nitrosourea

DFMO:

α-difluoromethylornithine

DMBA:

7,12-dimethylbenz[a]anthracene

eIF4E:

eukaryotic initiation factor 4E

ERK:

extracellular-signal-regulated kinase

5-FU:

5-fluorouracil

IFN:

interferon

IRES:

internal ribosome entry site

K14:

keratin 14

MEK:

mitogen-activated protein kinase kinase

mTOR:

mammalian target of rapamycin

NMBA:

N-nitrosomethylbenzylamine

ODC:

ornithine decarboxylase

OH-BBN:

N-butyl-N(4-hydroxybutyl)nitrosamine

SSAT:

spermidine/spermine N1-acetyltransferase

TPA:

12-O-tetradecanoylphorbol-13-acetate

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Authors and Affiliations

  1. Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA, USA

    L. M. Shantz

  2. The Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    V. A. Levin

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  1. L. M. Shantz
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  2. V. A. Levin
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Shantz, L., Levin, V. Regulation of ornithine decarboxylase during oncogenic transformation: mechanisms and therapeutic potential. Amino Acids 33, 213–223 (2007). https://doi.org/10.1007/s00726-007-0531-2

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  • DOI: https://doi.org/10.1007/s00726-007-0531-2

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