Nucleic acids differentially expressed between tumor and normal cells, useful for diagnosis or therapy of tumors and for screening active agents

摘要

A nucleic acid (I) with differential expression between tumor and normal cells comprising: (i) one of 550 fully defined sequences 250 nucleotides as given in the specification; (ii) fragments of (i) with at least 50, preferably 200 nucleotides; (iii) a sequence that hybridizes to (i) and/or (ii) under stringent conditions; or (iv) sequences complementary to (i)-(iii), is new. An independent claim is also included for testing the effect of active compounds (A) on gene expression by treating a cell line with (A), isolating and labeling cellular RNA and hybridizing it to an array to prepare a gene expression profile. - ACTIVITY : Cytostatic. - MECHANISM OF ACTION : Modulation of Ras activity by inducing expression of tumor suppressor genes. Differential expression analysis between FE-8 cells (rat fibroblasts transformed with H-ras) and normal 208F fibroblasts indicated differential expression of many hundreds of sequences. Treatment of the transformed cells with the MEK-specific inhibitor PD98059 resulted in a normal morphology and a significant reduction in capacity for anchorage-independent proliferation, despite a constant level of p21 ras. The inhibitor blocks the Raf/Mek signaling cascade and differential analysis of the treated cells showed that H-ras mediated down regulation of 36 transcripts was reversed and that upregulation of 25 transcripts was blocked. The amounts of mRNA from 116 genes or expressed sequences were not altered by the inhibitor.