A common regulation of genes encoding enzymes of the deoxynucleotide metabolism is lost after neoplastic transformation.
We determined the cell cycle-dependent fluctuation of mRNAs that encode different enzymes of the deoxynucleotide metabolism in permanent cell lines of human and murine origin. In normal growing cells, dihydrofolate reductase, thymidine kinase, and both subunits of ribonucleotide reductase all show exactly the same variation. The mRNAs rise near the G1-S boundary, peak in early S phase, and return in G2 to approximately the level of early G1. Deoxycytidine kinase mRNA does not follow this pattern, but remains essentially unchanged. Conversely, in DNA tumor virus-transformed cells, the levels of all these mRNAs remain relatively constant throughout all phases. These data provide evidence that DNA tumor viruses suppress a transcriptional down-regulation common to enzymes responsible for the DNA precursor pathway. The usefulness of analysis of mRNA levels of these genes for the detection of DNA tumor virus transformation is indicated.
Hengstschläger
M
M
Vienna Biocenter, University of Vienna, Austria.
Mudrak
I
I
Wintersberger
E
E
Wawra
E
E
D000818:Animals; D015152:Blotting, Northern; D002453:Cell Cycle; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D015342:DNA Probes; D003842:Deoxycytidine Kinase / Q000096:biosynthesis*; D003854:Deoxyribonucleotides / Q000378:metabolism*; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D004854:Herpesvirus 4, Human; D006801:Humans; D007668:Kidney; D007700:Kinetics; D008214:Lymphocytes / Q000166:cytology; D051379:Mice; D011120:Polyomavirus; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D012264:Ribonucleotide Reductases / Q000096:biosynthesis*; D013539:Simian virus 40; D013762:Tetrahydrofolate Dehydrogenase / Q000096:biosynthesis; D013937:Thymidine Kinase / Q000096:biosynthesis*; D013997:Time Factors
D015342:DNA Probes; D003854:Deoxyribonucleotides; D012333:RNA, Messenger; D012264:Ribonucleotide Reductases; D013762:Tetrahydrofolate Dehydrogenase; D013937:Thymidine Kinase; D003842:Deoxycytidine Kinase