In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 17 ( 2001-08-14), p. 9819-9823
Abstract:
Antisense oligodeoxynucleotides can selectively block
disease-causing genes, and cancer genes have been chosen as potential targets for antisense drugs to treat cancer. However, nonspecific side
effects have clouded the true antisense mechanism of action and hampered clinical development of antisense therapeutics. Using DNA
microarrays, we have conducted a systematic characterization of gene expression in cells exposed to antisense, either exogenously or
endogenously. Here, we show that in a sequence-specific manner, antisense targeted to protein kinase A RIα alters expression
of the clusters of coordinately expressed genes at a specific stage of cell growth, differentiation, and activation. The genes that define the
proliferation-transformation signature are down-regulated, whereas those that define the differentiation-reverse transformation signature
are up-regulated in antisense-treated cancer cells and tumors, but not in host livers. In this differentiation signature, the genes showing
the highest induction include genes for the G proteins Rap1 and Cdc42. The expression signature induced by the exogenously supplied antisense
oligodeoxynucleotide overlaps strikingly with that induced by endogenous antisense gene overexpression. Defining
antisense DNAs on the basis of their effects on global gene expression can lead to identification of clinically relevant
antisense therapeutics and can identify which molecular and cellular events might be important in complex biological processes,
such as cell growth and differentiation.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.171314398
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2001
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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