C-myc

Immediate early genes, e.g., c-fos, c-jun, and c-myc, are the first genes whose expression is induced in cells after a growth stimulus. They encode transcription factors and induce the expression of other growth-related genes. 

Growth inhibition by TGF- 3, associated with inhibition of c-myc, cdks, reduction in cyclin D1 levels, and inhibition of cdk-4-associated Rb kinase activity, as well as induction of cdk inhibitors pi5 and p27, has been noted in intestinal epithelial cells. Loss of responsiveness to growth inhibition from TGF- 3 occurs in many cell types including breast, colorectal carcinoma, and pancreatic carcinoma cells. Mutational inactivation of T 3RH represents one mechanism of this process, which in many cases, leads to the development of gastrointestinal cancer. Thirteen percent of colorectal carcinomas are thought to be associated with a replication error (RER) or microsatellite instability phenotype. Subsequent inactivation of T 3RII and... 

CuTRONA G., Carpaneto E.M., Ulivi M., Roncella S., Landt O., Ferrarini M., Boeea L. C. Effects in live cells of a c-myc anti-gene PNA linked to a nuclear localization signal. Nature Biotechnol. 

Jensen NA et al. Proteomic changes associated with degeneration of myelinforming cells in the central nervous system of c-myc transgenic mice. Electrophoresis 1998 19 2014-2020. 

Several cytoplasmic proteins capable of inducing T-cell growth (i.e. several cellular protooncogenes, including C-fos and C-myc). 

The less polar methyl ester 2 as prodrug showed better results in vivo and inhibits both farnesylation of the Ras protein and growth of Ras-transformed cells, whilst proliferation of Raf- or Mos-transformed cells was not influenced. Growth of human pancreatic adenocarcinoma cells with mutated K-Ras, c-Myc and p53 genes was inhibited by application of 2. If the compound is administered over a period of 5 days to mice with implanted Ras-dependent tumors, tumor growth can be reduced by up to 66% compared to untreated mice, whereas application of the antitumor antibiotic doxorubicin only resulted in 33% reduction under the same conditions. It is particularly noteworthy that treatment with the /1-turn mimetic - in contrast to treatment with doxorubicin - was without any visible side effects, such as weight loss. 

G-CSF expression is controlled at both the transcriptional and posttranscrip-tional levels. A sequence of 300 nucleotides upstream of the initiation codon is conserved in both the murine and human genes, and this appears to contain three regulatory sites. G-CSF (and some other cytokine genes) may be constitutively transcribed by cells such as blood monocytes, fibroblasts and endothelial cells, but the mRNA may be short-lived (fi/2 < 15 min). The mRNA contains poly-AUUUA sequences in the untranslated region, and this motif is usually associated with mRNA instability. Indeed, such regions have also been identified in mRNA for GM-CSF, IL-1, IL-6, interferons, TNF, some growth factors, c-jun, c-fos, c-myc and c-myb. Upon the addi-... 

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