Abstract
We have examined the role of the c-myc protooncogene in chemically induced differentiation of mouse erythroleukemia (MEL) cells by transfecting the cells with recombinant plasmids in which c-myc coding sequences were cloned downstream from the mouse metallothionein I promoter in sense and antisense orientations. We previously showed that treatment of MEL cells with inducers of differentiation leads to a rapid (less than 2 hr) decrease in the level of c-myc mRNA. c-myc mRNA is then transiently restored to pretreatment levels approximately 12-18 hr later. These events occur prior to the detection of cells that are irreversibly committed to erythroid differentiation. MEL cell transfectants containing the plasmid with myc in the sense orientation express a chimeric MT-myc mRNA, which also decreases shortly after addition of inducer. However, these clones reexpress myc RNA more rapidly than the parental line and they also differentiate more rapidly. On the other hand, transfectants containing the plasmid with myc in the antisense orientation exhibited a delay in the reexpression of c-myc mRNA and were found to differentiate more slowly than parental cells. Thus, we find a correlation between the time at which myc RNA is reexpressed following inducer treatment and the rate of entry of cells into the terminal differentiation program.
Full text
PDF![6480](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4ea/386527/df2719e26f99/pnas00321-0256.png)
![6481](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4ea/386527/2fb3baf06c1b/pnas00321-0257.png)
![6482](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4ea/386527/153e8b775d2e/pnas00321-0258.png)
![6483](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4ea/386527/37d78ab1305b/pnas00321-0259.png)
![6484](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4ea/386527/47a6d07b6b84/pnas00321-0260.png)
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Blanchard J. M., Piechaczyk M., Dani C., Chambard J. C., Franchi A., Pouyssegur J., Jeanteur P. c-myc gene is transcribed at high rate in G0-arrested fibroblasts and is post-transcriptionally regulated in response to growth factors. Nature. 1985 Oct 3;317(6036):443–445. doi: 10.1038/317443a0. [DOI] [PubMed] [Google Scholar]
- Coppola J. A., Cole M. D. Constitutive c-myc oncogene expression blocks mouse erythroleukaemia cell differentiation but not commitment. Nature. 1986 Apr 24;320(6064):760–763. doi: 10.1038/320760a0. [DOI] [PubMed] [Google Scholar]
- Fibach E., Reuben R. C., Rifkind R. A., Marks P. A. Effect of hexamethylene bisacetamide on the commitment to differentiation of murine erythroleukemia cells. Cancer Res. 1977 Feb;37(2):440–444. [PubMed] [Google Scholar]
- Ganguly S., Skoultchi A. I. Absolute rates of globin gene transcription and mRNA formation during differentiation of cultured mouse erythroleukemia cells. J Biol Chem. 1985 Oct 5;260(22):12167–12173. [PubMed] [Google Scholar]
- Gusella J., Geller R., Clarke B., Weeks V., Housman D. Commitment to erythroid differentiation by friend erythroleukemia cells: a stochastic analysis. Cell. 1976 Oct;9(2):221–229. doi: 10.1016/0092-8674(76)90113-6. [DOI] [PubMed] [Google Scholar]
- Hamer D. H., Walling M. Regulation in vivo of a cloned mammalian gene: cadmium induces the transcription of a mouse metallothionein gene in SV40 vectors. J Mol Appl Genet. 1982;1(4):273–288. [PubMed] [Google Scholar]
- Kelly K., Cochran B. H., Stiles C. D., Leder P. Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell. 1983 Dec;35(3 Pt 2):603–610. doi: 10.1016/0092-8674(83)90092-2. [DOI] [PubMed] [Google Scholar]
- Lachman H. M., Hatton K. S., Skoultchi A. I., Schildkraut C. L. c-myc mRNA levels in the cell cycle change in mouse erythroleukemia cells following inducer treatment. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5323–5327. doi: 10.1073/pnas.82.16.5323. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lachman H. M., Skoultchi A. I. Expression of c-myc changes during differentiation of mouse erythroleukaemia cells. Nature. 1984 Aug 16;310(5978):592–594. doi: 10.1038/310592a0. [DOI] [PubMed] [Google Scholar]
- Marks P. A., Rifkind R. A. Erythroleukemic differentiation. Annu Rev Biochem. 1978;47:419–448. doi: 10.1146/annurev.bi.47.070178.002223. [DOI] [PubMed] [Google Scholar]
- Müller R., Wagner E. F. Differentiation of F9 teratocarcinoma stem cells after transfer of c-fos proto-oncogenes. Nature. 1984 Oct 4;311(5985):438–442. doi: 10.1038/311438a0. [DOI] [PubMed] [Google Scholar]
- Noda M., Ko M., Ogura A., Liu D. G., Amano T., Takano T., Ikawa Y. Sarcoma viruses carrying ras oncogenes induce differentiation-associated properties in a neuronal cell line. Nature. 1985 Nov 7;318(6041):73–75. doi: 10.1038/318073a0. [DOI] [PubMed] [Google Scholar]
- Piechaczyk M., Yang J. Q., Blanchard J. M., Jeanteur P., Marcu K. B. Posttranscriptional mechanisms are responsible for accumulation of truncated c-myc RNAs in murine plasma cell tumors. Cell. 1985 Sep;42(2):589–597. doi: 10.1016/0092-8674(85)90116-3. [DOI] [PubMed] [Google Scholar]
- Potter H., Weir L., Leder P. Enhancer-dependent expression of human kappa immunoglobulin genes introduced into mouse pre-B lymphocytes by electroporation. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7161–7165. doi: 10.1073/pnas.81.22.7161. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Soeiro R., Darnell J. E. Competition hybridization by "pre-saturation" of HeLa cell DNA. J Mol Biol. 1969 Sep 28;44(3):551–562. doi: 10.1016/0022-2836(69)90379-9. [DOI] [PubMed] [Google Scholar]
- Southern P. J., Berg P. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet. 1982;1(4):327–341. [PubMed] [Google Scholar]
- Stanton L. W., Fahrlander P. D., Tesser P. M., Marcu K. B. Nucleotide sequence comparison of normal and translocated murine c-myc genes. Nature. 1984 Aug 2;310(5976):423–425. doi: 10.1038/310423a0. [DOI] [PubMed] [Google Scholar]
- Stanton L. W., Watt R., Marcu K. B. Translocation, breakage and truncated transcripts of c-myc oncogene in murine plasmacytomas. Nature. 1983 Jun 2;303(5916):401–406. doi: 10.1038/303401a0. [DOI] [PubMed] [Google Scholar]
- Velcich A., Ziff E. Adenovirus E1a proteins repress transcription from the SV40 early promoter. Cell. 1985 Mar;40(3):705–716. doi: 10.1016/0092-8674(85)90219-3. [DOI] [PubMed] [Google Scholar]