Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.5.1.3 (dihydrofolate reductase)
 5,819 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have analysed relative DHFR gene copy numbers in nine cell lines of various cell type and species origins. The cells studied expressed either low, low and inducible or constitutively elevated levels of c-Myc protein. DHFR gene amplification was observed only when c-Myc protein levels were upregulated. The amplification of the DHFR gene was transient in inducible cell lines. Cell lines exhibiting constitutively deregulated c-Myc protein levels, however, showed both DHFR gene amplification and ongoing rearrangements of the DHFR locus. In contrast, the relative gene copy numbers of ribonucleotide reductase R1 subunit, ornithine decarboxylase, syndecan 2, glyceraldehyde-3-phosphate-dehydrogenase, and cyclin C remained unaffected irrespective of c-Myc protein levels, suggesting a locus-specific genomic instability of the DHFR gene in cells with deregulated c-Myc protein levels. Overall, the results of the present study support the notion that DHFR gene amplification as a consequence of c-Myc deregulation may occur in a variety of cell lines irrespective of their cell type and species origins.
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PMID:c-Myc overexpression associated DHFR gene amplification in hamster, rat, mouse and human cell lines. 857 Feb 5

Murine Pre-B lymphocytes with experimentally activated MycER show both chromosomal and extrachromosomal gene amplification. In this report, we have elucidated the size, structure, and functional components of c-Myc-induced extrachromosomal elements (EEs). Scanning electron microscopy revealed that EEs isolated from MycER-activated Pre-B+ cells are an average of 10 times larger than EEs isolated from non-MycER-activated control Pre-B- cells. We demonstrate that these large c-Myc-induced EEs are associated with histone proteins, whereas EEs of non-MycER-activated Pre B- cells are not. Immunohistochemistry and Western blot analyses using pan-histone-specific, histone H3 phosphorylation-specific, and histone H4 acetylation-specific antibodies indicate that a significant proportion of EEs analyzed from MycER-activated cells harbors transcriptionally competent and/or active chromatin. Moreover, these large, c-Myc-induced EEs carry genes. Whereas the total genetic make-up of these c-Myc-induced EEs is unknown, we found that 30.2% of them contain the dihydrofolate reductase (DHFR) gene, whereas cyclin C (CCNC) was absent. In addition, 50% of these c-Myc-activated Pre-B+ EEs incorporated bromodeoxyuridine (BrdU), identifying them as genetic structures that self-propagate. In contrast, EEs isolated from non-Myc-activated cells neither carry the DHFR gene nor incorporate BrdU, suggesting that c-Myc deregulation generates a new class of EEs.
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PMID:c-Myc-induced extrachromosomal elements carry active chromatin. 1265 83