Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1985 Aug;82(16):5375–5379. doi: 10.1073/pnas.82.16.5375

Expression of cell-cycle-dependent genes in phytohemagglutinin-stimulated human lymphocytes.

L Kaczmarek, B Calabretta, R Baserga
PMCID: PMC390571  PMID: 2410921

Abstract

We have investigated the expression of certain cell-cycle-dependent genes in human peripheral blood mononuclear cells (PBMC) stimulated by phytohemagglutinin (PHA). The genes studied had been previously identified as cell-cycle dependent in other cell types from different species and were induced by different mitogens. One of these genes (2F1) and the gene for the interleukin 2 receptor were induced by PHA even in cultures partially depleted of accessory cells where the lymphocytes grew in size but failed to enter S phase. The other genes (c-myc, 4F1, JE-3, and KC-1) were induced only in complete cultures of PBMC stimulated by PHA. These results confirm the dissociation between growth in size and cell DNA replication that can occur during cell-cycle progression. Moreover, the time course of appearance of detectable levels of RNA for these genes suggests that they may be used as markers of cell-cycle progression in the transition of lymphocytes from G0 to S phase.

Full text

PDF
5376

Images in this article

5376Image
on p.5376
5376Image
on p.5376
5377Image
on p.5377
5377Image
on p.5377
5378Image
on p.5378

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Artishevsky A., Delegeane A. M., Lee A. S. Use of a cell cycle mutant to delineate the critical period for the control of histone mRNA levels in the mammalian cell cycle. Mol Cell Biol. 1984 Nov;4(11):2364–2369. doi: 10.1128/mcb.4.11.2364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arya S. K., Wong-Staal F., Gallo R. C. Transcriptional regulation of a tumor promoter and mitogen-inducible gene in human lymphocytes. Mol Cell Biol. 1984 Nov;4(11):2540–2542. doi: 10.1128/mcb.4.11.2540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baserga R. Growth in size and cell DNA replication. Exp Cell Res. 1984 Mar;151(1):1–5. doi: 10.1007/978-3-642-67986-5_1. [DOI] [PubMed] [Google Scholar]
  4. Bettens F., Kristensen F., Walker C., Bonnard G. D., de Weck A. L. Lymphokine regulation of human lymphocyte proliferation: formation of resting G0 cells by removal of interleukin 2 in cultures of proliferating T lymphocytes. Cell Immunol. 1984 Jul;86(2):337–346. doi: 10.1016/0008-8749(84)90388-5. [DOI] [PubMed] [Google Scholar]
  5. Calabretta B., Kaczmarek L., Mars W., Ochoa D., Gibson C. W., Hirschhorn R. R., Baserga R. Cell-cycle-specific genes differentially expressed in human leukemias. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4463–4467. doi: 10.1073/pnas.82.13.4463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Campisi J., Gray H. E., Pardee A. B., Dean M., Sonenshein G. E. Cell-cycle control of c-myc but not c-ras expression is lost following chemical transformation. Cell. 1984 Feb;36(2):241–247. doi: 10.1016/0092-8674(84)90217-4. [DOI] [PubMed] [Google Scholar]
  7. Cantrell D. A., Smith K. A. The interleukin-2 T-cell system: a new cell growth model. Science. 1984 Jun 22;224(4655):1312–1316. doi: 10.1126/science.6427923. [DOI] [PubMed] [Google Scholar]
  8. Chafouleas J. G., Lagacé L., Bolton W. E., Boyd A. E., 3rd, Means A. R. Changes in calmodulin and its mRNA accompany reentry of quiescent (G0) cells into the cell cycle. Cell. 1984 Jan;36(1):73–81. doi: 10.1016/0092-8674(84)90075-8. [DOI] [PubMed] [Google Scholar]
  9. Cochran B. H., Reffel A. C., Stiles C. D. Molecular cloning of gene sequences regulated by platelet-derived growth factor. Cell. 1983 Jul;33(3):939–947. doi: 10.1016/0092-8674(83)90037-5. [DOI] [PubMed] [Google Scholar]
  10. Cochran B. H., Zullo J., Verma I. M., Stiles C. D. Expression of the c-fos gene and of an fos-related gene is stimulated by platelet-derived growth factor. Science. 1984 Nov 30;226(4678):1080–1082. doi: 10.1126/science.6093261. [DOI] [PubMed] [Google Scholar]
  11. Dalla-Favera R., Bregni M., Erikson J., Patterson D., Gallo R. C., Croce C. M. Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7824–7827. doi: 10.1073/pnas.79.24.7824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dalla-Favera R., Gelmann E. P., Martinotti S., Franchini G., Papas T. S., Gallo R. C., Wong-Staal F. Cloning and characterization of different human sequences related to the onc gene (v-myc) of avian myelocytomatosis virus (MC29). Proc Natl Acad Sci U S A. 1982 Nov;79(21):6497–6501. doi: 10.1073/pnas.79.21.6497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Darzynkiewicz Z., Evenson D. P., Staiano-Coico L., Sharpless T. K., Melamed M. L. Correlation between cell cycle duration and RNA content. J Cell Physiol. 1979 Sep;100(3):425–438. doi: 10.1002/jcp.1041000306. [DOI] [PubMed] [Google Scholar]
  14. Darzynkiewicz Z., Sharpless T., Staiano-Coico L., Melamed M. R. Subcompartments of the G1 phase of cell cycle detected by flow cytometry. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6696–6699. doi: 10.1073/pnas.77.11.6696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. DeLisle A. J., Graves R. A., Marzluff W. F., Johnson L. F. Regulation of histone mRNA production and stability in serum-stimulated mouse 3T6 fibroblasts. Mol Cell Biol. 1983 Nov;3(11):1920–1929. doi: 10.1128/mcb.3.11.1920. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Doolittle R. F., Hunkapiller M. W., Hood L. E., Devare S. G., Robbins K. C., Aaronson S. A., Antoniades H. N. Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science. 1983 Jul 15;221(4607):275–277. doi: 10.1126/science.6304883. [DOI] [PubMed] [Google Scholar]
  17. Downward J., Yarden Y., Mayes E., Scrace G., Totty N., Stockwell P., Ullrich A., Schlessinger J., Waterfield M. D. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature. 1984 Feb 9;307(5951):521–527. doi: 10.1038/307521a0. [DOI] [PubMed] [Google Scholar]
  18. Efrat S., Kaempfer R. Control of biologically active interleukin 2 messenger RNA formation in induced human lymphocytes. Proc Natl Acad Sci U S A. 1984 May;81(9):2601–2605. doi: 10.1073/pnas.81.9.2601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Eliyahu D., Raz A., Gruss P., Givol D., Oren M. Participation of p53 cellular tumour antigen in transformation of normal embryonic cells. Nature. 1984 Dec 13;312(5995):646–649. doi: 10.1038/312646a0. [DOI] [PubMed] [Google Scholar]
  20. Foster D. N., Schmidt L. J., Hodgson C. P., Moses H. L., Getz M. J. Polyadenylylated RNA complementary to a mouse retrovirus-like multigene family is rapidly and specifically induced by epidermal growth factor stimulation of quiescent cells. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7317–7321. doi: 10.1073/pnas.79.23.7317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Frazier M. L., Mars W., Florine D. L., Montagna R. A., Saunders G. F. Efficient extraction of RNA from mammalian tissue. Mol Cell Biochem. 1983;56(2):113–122. doi: 10.1007/BF00227211. [DOI] [PubMed] [Google Scholar]
  22. Gathings W. E., Lawton A. R., Cooper M. D. Immunofluorescent studies of the development of pre-B cells, B lymphocytes and immunoglobulin isotype diversity in humans. Eur J Immunol. 1977 Nov;7(11):804–810. doi: 10.1002/eji.1830071112. [DOI] [PubMed] [Google Scholar]
  23. Goyette M., Petropoulos C. J., Shank P. R., Fausto N. Expression of a cellular oncogene during liver regeneration. Science. 1983 Feb 4;219(4584):510–512. doi: 10.1126/science.6297003. [DOI] [PubMed] [Google Scholar]
  24. Goyette M., Petropoulos C. J., Shank P. R., Fausto N. Regulated transcription of c-Ki-ras and c-myc during compensatory growth of rat liver. Mol Cell Biol. 1984 Aug;4(8):1493–1498. doi: 10.1128/mcb.4.8.1493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Greenberg M. E., Ziff E. B. Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature. 1984 Oct 4;311(5985):433–438. doi: 10.1038/311433a0. [DOI] [PubMed] [Google Scholar]
  26. Hirschhorn R. R., Aller P., Yuan Z. A., Gibson C. W., Baserga R. Cell-cycle-specific cDNAs from mammalian cells temperature sensitive for growth. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6004–6008. doi: 10.1073/pnas.81.19.6004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  28. Koretzky G. A., Daniele R. P., Greene W. C., Nowell P. C. Evidence for an interleukin-independent pathway for human lymphocyte activation. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3444–3447. doi: 10.1073/pnas.80.11.3444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kruijer W., Cooper J. A., Hunter T., Verma I. M. Platelet-derived growth factor induces rapid but transient expression of the c-fos gene and protein. Nature. 1984 Dec 20;312(5996):711–716. doi: 10.1038/312711a0. [DOI] [PubMed] [Google Scholar]
  30. Lai E. C., Woo S. L., Dugaiczyk A., O'Malley B. W. The ovalbumin gene: alleles created by mutations in the intervening sequences of the natural gene. Cell. 1979 Jan;16(1):201–211. doi: 10.1016/0092-8674(79)90201-0. [DOI] [PubMed] [Google Scholar]
  31. Leder P., Battey J., Lenoir G., Moulding C., Murphy W., Potter H., Stewart T., Taub R. Translocations among antibody genes in human cancer. Science. 1983 Nov 18;222(4625):765–771. doi: 10.1126/science.6356357. [DOI] [PubMed] [Google Scholar]
  32. Leonard W. J., Depper J. M., Crabtree G. R., Rudikoff S., Pumphrey J., Robb R. J., Krönke M., Svetlik P. B., Peffer N. J., Waldmann T. A. Molecular cloning and expression of cDNAs for the human interleukin-2 receptor. Nature. 1984 Oct 18;311(5987):626–631. doi: 10.1038/311626a0. [DOI] [PubMed] [Google Scholar]
  33. Linzer D. I., Nathans D. Growth-related changes in specific mRNAs of cultured mouse cells. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4271–4275. doi: 10.1073/pnas.80.14.4271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Liu H. T., Gibson C. W., Hirschhorn R. R., Rittling S., Baserga R., Mercer W. E. Expression of thymidine kinase and dihydrofolate reductase genes in mammalian ts mutants of the cell cycle. J Biol Chem. 1985 Mar 25;260(6):3269–3274. [PubMed] [Google Scholar]
  35. Maizel A. L., Mehta S. R., Hauft S., Franzini D., Lachman L. B., Ford R. J. Human T lymphocyte/monocyte interaction in response to lectin: kinetics of entry into the S-phase. J Immunol. 1981 Sep;127(3):1058–1064. [PubMed] [Google Scholar]
  36. Maizel A. L., Mehta S., Ford R. J. T-lymphocyte/monocyte interaction in response to phytohemagglutinin. Cell Immunol. 1979 Dec;48(2):383–397. doi: 10.1016/0008-8749(79)90133-3. [DOI] [PubMed] [Google Scholar]
  37. Makino R., Hayashi K., Sugimura T. C-myc transcript is induced in rat liver at a very early stage of regeneration or by cycloheximide treatment. Nature. 1984 Aug 23;310(5979):697–698. doi: 10.1038/310697a0. [DOI] [PubMed] [Google Scholar]
  38. McCairns E., Fahey D., Muscat G. E., Murray M., Rowe P. B. Changes in levels of actin and tubulin mRNAs upon the lectin activation of lymphocytes. Mol Cell Biol. 1984 Sep;4(9):1754–1760. doi: 10.1128/mcb.4.9.1754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Müller R., Bravo R., Burckhardt J., Curran T. Induction of c-fos gene and protein by growth factors precedes activation of c-myc. Nature. 1984 Dec 20;312(5996):716–720. doi: 10.1038/312716a0. [DOI] [PubMed] [Google Scholar]
  40. Neckers L. M., Cossman J. Transferrin receptor induction in mitogen-stimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleukin 2. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3494–3498. doi: 10.1073/pnas.80.11.3494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Plumb M., Stein J., Stein G. Coordinate regulation of multiple histone mRNAs during the cell cycle in HeLa cells. Nucleic Acids Res. 1983 Apr 25;11(8):2391–2410. doi: 10.1093/nar/11.8.2391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Reich N. C., Levine A. J. Growth regulation of a cellular tumour antigen, p53, in nontransformed cells. Nature. 1984 Mar 8;308(5955):199–201. doi: 10.1038/308199a0. [DOI] [PubMed] [Google Scholar]
  43. Rothberg P. G., Erisman M. D., Diehl R. E., Rovigatti U. G., Astrin S. M. Structure and expression of the oncogene c-myc in fresh tumor material from patients with hematopoietic malignancies. Mol Cell Biol. 1984 Jun;4(6):1096–1103. doi: 10.1128/mcb.4.6.1096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Ruscetti F. W., Gallo R. C. Human T-lymphocyte growth factor: regulation of growth and function of T lymphocytes. Blood. 1981 Mar;57(3):379–394. [PubMed] [Google Scholar]
  45. Slamon D. J., deKernion J. B., Verma I. M., Cline M. J. Expression of cellular oncogenes in human malignancies. Science. 1984 Apr 20;224(4646):256–262. doi: 10.1126/science.6538699. [DOI] [PubMed] [Google Scholar]
  46. Talavera A., Basilico C. Temperature sensitive mutants of BHK cells affected in cell cycle progression. J Cell Physiol. 1977 Sep;92(3):425–436. doi: 10.1002/jcp.1040920310. [DOI] [PubMed] [Google Scholar]
  47. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Waterfield M. D., Scrace G. T., Whittle N., Stroobant P., Johnsson A., Wasteson A., Westermark B., Heldin C. H., Huang J. S., Deuel T. F. Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature. 1983 Jul 7;304(5921):35–39. doi: 10.1038/304035a0. [DOI] [PubMed] [Google Scholar]
  49. Williams J. M., Ransil B. J., Shapiro H. M., Strom T. B. Accessory cell requirement for activation antigen expression and cell cycle progression by human T lymphocytes. J Immunol. 1984 Dec;133(6):2986–2995. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES