ORNITHINE DECARBOXYLASE ACTIVITY IS CRITICAL FOR CELL-TRANSFORMATION

Article

关键词: ROUS-SARCOMA VIRUS;    POLYAMINE METABOLISM;    GENE-EXPRESSION;    TYROSINE;    GROWTH;    PHOSPHORYLATION;    AMPLIFICATION;    INDUCTION;    KINASES;    DNA;   

DOI  :  10.1038/360355a0

来源: SCIE

【 摘 要 】

THE enzyme ornithine decarboxylase is the key regulator of the synthesis of polyamines1-3 which are essential for cell proliferation4,5. Expression of this enzyme is transiently increased upon stimulation by growth factors1-3, but becomes constitutively activated during cell transformation induced by carcinogens6,7, viruses8-10 or oncogenes11-14. To test whether ornithine decarboxylase could be a common mediator of transformation and oncogenic itself, we transfected NIH3T3 cells with expression vectors carrying the complementary DNA encoding human ornithine decarboxylase in sense and antisense orientations. The increased expression of the enzyme (50-100-times endogenous levels) induced not only cell transformation, but also anchorage-independent growth in soft agar and increased tyrosine phosphorylation of a protein of M(r) 130K. Expression of ornithine decarboxylase antisense RNA was associated with an epithelioid morphology and reduced cell proliferation. Moreover, blocking the endogenous enzyme using specific inhibitor or synthesizing antisense RNA prevented transformation of rat fibroblasts by temperature-sensitive v-src oncogene. Our results imply that the gene encoding ornithine decarboxylase is a proto-oncogene central for regulation of cell growth and transformation.

【 授权许可】

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