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Science 31 May 1985:
Vol. 228. no. 4703, pp. 1099 - 1101
DOI: 10.1126/science.2581317

Articles

Science, Vol 228, Issue 4703, 1099-1101
Copyright © 1985 by American Association for the Advancement of Science


articles

Reversibility of progression of the transformed phenotype in Ad5-transformed rat embryo cells

LE Babiss, SG Zimmer, and PB Fisher

The carcinogenic process is extremely complex and is affected by diverse environmental and host factors. The mechanism for the gradual development of the transformed phenotype (a process termed "progression") was studied in type 5 adenovirus (Ad5)-transformed rat embryo cells. Progression was not correlated with major changes in the pattern of integration of viral DNA sequences. Instead, it was associated with an increased methylation of integrated viral sequences other than those corresponding to the E1 transforming genes of Ad5. A single exposure of progressed cells to the demethylating agent 5-azacytidine (Aza) resulted in a stable reversion to the unprogressed state of the original parental clone. A further selection of cells after growth in agar allowed the isolation of Aza-treated clones that had regained the progressed phenotype. These observations indicate that progression is a reversible process and suggest that progression may be associated with changes in the state of methylation of one or more specific genes.


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Targeting gene expression selectively in cancer cells by using the progression-elevated gene-3 promoter.
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PEA3 sites within the progression elevated gene-3 (PEG-3) promoter and mitogen-activated protein kinase contribute to differential PEG-3 expression in Ha-ras and v-raf oncogene transformed rat embryo cells.
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PEG-3, a nontransforming cancer progression gene, is a positive regulator of cancer aggressiveness and angiogenesis.
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Reciprocal subtraction differential RNA display: An efficient and rapid procedure for isolating differentially expressed gene sequences.
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Antisense inhibition of the PTI-1 oncogene reverses cancer phenotypes.
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Subtraction hybridization identifies a transformation progression-associated gene PEG-3 with sequence homology to a growth arrest and DNA damage-inducible gene.
Z.-Z. Su, Y. Shi, and P. B. Fisher (1997)
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Science. ISSN 0036-8075 (print), 1095-9203 (online)