Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Interleukin-2 expression in human carcinoma cell lines and its role in cell cycle progression

Oncogene volume 19, pages 514–525 (2000)Cite this article

Abstract

Human carcinomas were shown to express mRNA and protein for IL-2R α, β and γ chains. Recently, human carcinomas were also shown to constitutively express protein and mRNA for IL-2 in vivo and in vitro. Here we report that the expression levels of cytoplasmic IL-2 as well as IL-2Rβ- and γ-chain in human carcinoma cells change during the cell cycle progression. Carcinoma cells synchronized in the G2/M phase of the cell cycle expressed significantly more intracytoplasmic IL-2 as well as IL-2Rβ and γ proteins than tumor cells in the G0/G1 phase. The level of mRNA for IL-2 was 5–10-fold higher in the M phase than in the G0/G1-phase, as shown by quantitative competitive RT–PCR. Expression of the cyclin-dependent kinase (CDK) inhibitor p27kip1 in these carcinoma cells was found to be high in the G0/G1 phase, nearly absent in the S phase, and it increased again in the G2/M phase of the cell cycle. In synchronized cells, the decrease in p27 expression coincided with high levels of expression of IL-2. Using the IL-2 specific antisense oligonucleotide to block synthesis of endogenous IL-2 in tumor cells, we observed increased levels of p27 as well as p21. The antisense oligonucleotides specific for p27 or p21 blocked expression of these proteins but not of IL-2. Thus, endogenous IL-2 is important in regulating expression of p27 as well as p21 and, therefore, in controlling cell cycle progression of tumor cells, while its own expression remains independent of the CDK inhibitors.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9

Similar content being viewed by others

Abbreviations

ASO:

antisense oligonucleotide

CDK:

cyclin-dependent kinase

Con A:

Concanavalin A

HR:

human gastric carcinoma

IL-2:

Interleukin-2

IL-2R:

Interleukin-2 receptor

IP:

immunoperoxidase

p27:

a CDK inhibitor, also called Kip1

PBL:

peripheral blood lymphocytes

PBMC:

peripheral blood mononuclear cells

PHA:

phytohemagglutinin

PI:

propidium iodide

RT–PCR:

reverse-transcription polymerase chain reaction

SCCHN:

squamous cell carcinoma of the head and neck

References

  • Alberts B, Bray D, Lewis J, Raff M, Roberts K and Watson JD. . 1994 The Mechanics of Cell Division. In: Alberts B, Bray D, Lewis J, Raff M, Roberts K and Watson JD (eds). Molecular Biology of the Cell, 3rd edition New York: Garland Publishing, Inc. pp. 911–946.

    Google Scholar 

  • Alileche A, Plaisance S, Han DS, Rubinstein, E, Mingari C, Bellomo R, Jasmin C and Azzarone B. . 1993 Oncogene 8: 1791–1796.

  • Alileche A, Han D, Plaisance S, Assier E, Sahraoui Y, Clemanceau C, Metivier D, Brouty-Boyer D, Jasmin C and Azzarone B. . 1994 Int. Immunol. 6: 1585–1591.

  • Arzt E, Stelzer G, Renner U, Lange M, Muller OA and Stalla GK. . 1992 J. Clin. Invest. 90: 1944–1951.

  • Bouaboula M, Legoux P, Pessegue B, Delpech B, Dumont X, Piechaczyk M, Casellas P and Shire D. . 1992 J. Biol. Chem. 267: 21830–21838.

  • Chen K, Demetris AJ, Van Thiel DH and Whiteside TL. . 1987 Lab. Invest. 56: 114–119.

  • Chomczynski P and Sacchi N. . 1987 Anal. Biochem. 162: 156–159.

  • Ciacci C, Mahida YR, Dignass A, Koizumi M and Podolsky DK. . 1993 J. Clin. Invest. 92: 527–532.

  • Duprez V, Cornet V and Dautry-Versat A. . 1988 J. Biol. Chem. 263: 12860–12865.

  • Hatakeyama M and Taniguchi T. . 1990 Interleukin-2. In: Sporn MB and Roberts AB (eds). Peptide Growth Factors and Their Receptors 1. New York: Springer-Verlag. pp. 523.

    Google Scholar 

  • Hemar A, Lieb M, Subtil A, DiSanto JP and Dautry-Varsat A. . 1994 Eur. J. Immunol. 24: 1951–1955.

  • Heo DS, Snyderman C, Gollin SM, Pan S, Walker E, Deka R, Barnes EL, Johnson JT, Herberman RB and Whiteside TL. . 1989 Cancer Res. 49: 5167–5175.

  • Huberman JA. . 1981 Cell 23: 647–648.

  • Lai P, Rabinowich H, Crowley-Nowick PA, Bell MC, Mantovani G and Whiteside TL. . 1996 Clin. Cancer Res. 2: 161–173.

  • Lin WC, Yasumura S, Suminami Y, Sung MW, Nagashima S, Stanson J and Whiteside TL. . 1995 J. Immunol. 155: 4805–4816.

  • Liu J, Flanagan M, Drazba JA, Estes ML, Barnett GH, Haqqi T, Kondo S, Barna BP. . 1997 J. Immunol. 159: 812–819.

  • McMillan DN, Kernohan NM, Flett ME, Heys SD, Deehan DJ, Sewell HF, Walker F and Eremin O. . 1995 Int. J. Cancer. 60: 766–772.

  • Miyazaki M, Ohashi R, Tsuji T, Mihara L, Gohda E, Namba M. . 1998 BBRC 246: 873-880.

  • Nakanishi K, Hirose S, Yoshimoto T, Ishizashi H, Hiroishi K, Tanaka T, Kono T, Miyasaka M, Taniguchi T and Higashino K. . 1992 Proc. Natl. Acad. Sci. USA 89: 3551–3555.

  • Nourse J, Firpo E, Flanagan WM, Coats S, Polyak K, Lee M-H, Massaque J, Crabtree GR, Roberts JM. . 1994 Nature 382: 570–573.

  • O’Connor PM and Jackman J. . 1995 Synchronization of mammalian cells. In: Paano M (ed.). Cell Cycle–Materials and Methods. Berlin Heidelberg: Springer-Verlag. pp. 63–74.

    Google Scholar 

  • Pardee AB. . 1989 Science 246: 603–608.

  • Plaisance S, Rubinstein E, Alileche A, Sahraouri Y, Krief P, Augrey-Bourget Y, Jasmin C, Suarez H, Azzarone B. . 1992 Int. Immunol. 4: 739–746.

  • Plaisance S, Rubinstein E, Alileche A, Benoit P, Jasmin C and Azzarone B. . 1993 Int. Immunol. 5: 843–848.

  • Rabinowich H, Vitolo D, Altarac S, Herberman RB and Whiteside TL. . 1992 J. Immunol. 149: 340–349.

  • Ralph P, Jeong G, Welte K, Mertelsmann R, Rabin H, Henderson LE, Souza LM, Boone TC and Robb RL. . 1984 J. Immunol. 133: 2442–2445.

  • Reichert TE, Watkins S, Stanson J, Johnson JT, Whiteside TL. . 1998 J. Histochem. Cytochem. 46: 603–611.

  • Reichert TE, Kashii Y, Stanson J, Zeevi A, Whiteside TL. . 1999 Br. J. Cancer. 81: 822–831.

  • Rimoldi D, Salvi S, Hartmann F, Schreyer M, Blum S, Zografos L, Plaisance S, Azzarone B and Carrel S. . 1993 Anticancer Res. 13: 555–564.

  • Robb RJ, Greene WC and Rusk CM. . 1984 J. Exp. Med. 160: 1126–1146.

  • Sander B, Anderson J and Andersson U. . 1991 Immunol. Rev. 119: 65–93.

  • Saneto RP, Altman A, Knobler RL, Johnson HM and DeVellis Y. . 1986 Proc. Natl. Acad. Sci. USA 83: 9221–9225.

  • Seigel LJ, Harper ME, Wong-Staal F, Gallo RC, Nash WG and SI OB. . 1984 Science 223: 175–178.

  • Shimizu Y, Weidmann E, Iwatsuki S, Herberman RB and Whiteside TL. . 1991 Cancer Res. 51: 6153–6162.

  • Stern JB and Smith KA. . 1986 Science 233: 203–206.

  • Suminami Y, Elder EM, Lotze MT, Whiteside TL. . 1995 J. Immunother. 17: 238–248.

  • Suminami Y, Kashii Y, Law JC, Lin W-C, Stanson J, Reichert TE, Rabinowich H, Whiteside TL. . 1998 Oncogene 16: 1309–1317.

  • Takeshita T, Asao H, Ohtani K, Ishii N, Kumaki S, Tanaka N, Munakata H, Nakamura M and Sugamura K. . 1992 Science 257: 379–382.

  • Takeshita T, Goto Y, Tada K, Nagata K, Asao H and Sugamura K. . 1989 J. Exp. Med. 169: 1323–1332.

  • Taniguchi T and Minami Y. . 1993 Cell 73: 5–8.

  • Waldmann TA. . 1991 J. Biol. Chem. 266: 2681.

  • Weidmann E, Sacchi M, Plaisance S, Heo DS, Yasumura S, Lin WC, Johnson JT, Herberman RB, Azzarone B and Whiteside TL. . 1992 Cancer Res. 52: 5963–5970.

  • Whiteside TL and Herberman RB. . 1995 Curr. Opin. Immunol. 7: 704–710.

  • Yasumura S, Lin WC, Weidmann E, Hebda P and Whiteside TL. . 1994 Int. J. Cancer 59: 225–234.

Download references

Acknowledgements

This work was supported in part by R0-1 CA 63513 to TL Whiteside. TE Reichert was supported by the Deutsche Forschungsgemeinschaft (DFG), Grant Re 1155/1-1.

Author information

Authors and Affiliations

  1. University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, 15213, PA, USA

    Torsten E Reichert, Shigeki Nagashima, Yoshiro Kashii, Joanna Stanson & Theresa L Whiteside

  2. Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, 15213, PA, USA

    Theresa L Whiteside

  3. Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, 15213, PA, USA

    Theresa L Whiteside

  4. Department of Biochemistry, H Lee Moffitt Cancer Center & Research Institute, Tampa, 33612, Florida, FL, USA

    Gui Gao & Qing Ping Dou

  5. Department of Molecular Biology, H Lee Moffitt Cancer Center & Research Institute, Tampa, 33612, Florida, FL, USA

    Gui Gao & Qing Ping Dou

Authors
  1. Torsten E Reichert
    View author publications

    Search author on:PubMed Google Scholar

  2. Shigeki Nagashima
    View author publications

    Search author on:PubMed Google Scholar

  3. Yoshiro Kashii
    View author publications

    Search author on:PubMed Google Scholar

  4. Joanna Stanson
    View author publications

    Search author on:PubMed Google Scholar

  5. Gui Gao
    View author publications

    Search author on:PubMed Google Scholar

  6. Qing Ping Dou
    View author publications

    Search author on:PubMed Google Scholar

  7. Theresa L Whiteside
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reichert, T., Nagashima, S., Kashii, Y. et al. Interleukin-2 expression in human carcinoma cell lines and its role in cell cycle progression. Oncogene 19, 514–525 (2000). https://doi.org/10.1038/sj.onc.1203391

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/sj.onc.1203391

Keywords

This article is cited by

Search

Advanced search

Quick links