TY - JOUR
T1 - Regulation of ornithine decarboxylase during oncogenic transformation
T2 - Mechanisms and therapeutic potential
AU - Shantz, L. M.
AU - Levin, V. A.
PY - 2007/8
Y1 - 2007/8
N2 - 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.
AB - 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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U2 - 10.1007/s00726-007-0531-2
DO - 10.1007/s00726-007-0531-2
M3 - Review article
C2 - 17443268
AN - SCOPUS:34547669262
SN - 0939-4451
VL - 33
SP - 213
EP - 223
JO - Amino Acids
JF - Amino Acids
IS - 2
ER -