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:

Gene expression profiles in HTLV-I-immortalized T cells: deregulated expression of genes involved in apoptosis regulation

Oncogene volume 18, pages 1341–1349 (1999)Cite this article

Abstract

Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia, an acute and often fatal T-cell malignancy. A key step in HTLV-I-induced leukemigenesis is induction of abnormal T-cell growth and survival. Unlike antigen-stimulated T cells, which cease proliferation after a finite number of cell division, HTLV-I-infected T cells proliferate indefinitely (immortalized), thus facilitating occurrence of secondary genetic changes leading to malignant transformation. To explore the molecular basis of HTLV-I-induced abnormal T-cell survival, we compared the gene expression profiles of normal and HTLV-I-immortalized T cells using `gene array'. These studies revealed a strikingly altered expression pattern of a large number of genes along with HTLV-I-mediated T-cell immortalization. Interestingly, many of these deregulated genes are involved in the control of programmed cell death or apoptosis. These findings indicate that disruption of the cellular apoptosis-regulatory network may play a role in the HTLV-I-mediated oncogenesis.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1
Figure 2

Similar content being viewed by others

References

  • Akagi T, Ono H and Shimotohno K. . 1997 Leukemia 11: Suppl 3 25.

  • Alexandre C and Verrier B. . 1991 Oncogene 6: 543–551.

  • Arai M, Kannagi M, Matsuoka M, Sato T, Yamamoto N and Fujii M. . 1998 AIDS Res. Hum. Retroviruses 14: 261–267.

  • Bargou RC, Jurchott K, Wagener C, Bergmann S, Metzner S, Bommert K, Mapara MY, Winzer KJ, Dietel M, Dorken B and Royer HD. . 1997 Nat. Med. 3: 447–450.

  • Baum PR, Gayle RB, Ramsdell F, Srinivasan S, Sorensen RA, Watson ML, Seldin MF, Baker E, Sutherland GR, Clifford KN, Alderson MR, Goodwin RG and Fanslow WC. . 1994 EMBO J. 13: 3992–4001.

  • Boise LH, Gonzalez-Garcia M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nunez G and Thompson CB. . 1993 Cell 74: 597–608.

  • Boldin MP, Goncharov TM, Goltsev YV and Wallach D. . 1996 Cell 85: 803–815.

  • Brauweiler A, Garrus JE, Reed JC and Nyborg JK. . 1997 Virology 231: 135–140.

  • Browning JL, Dougas I, Ngam-ek A, Bourdon PR, Ehrenfels BN, Miatkowski K, Zafari M, Yampaglia AM, Lawton P, Meier W, Benjamin CP and Hession C. . 1995 J. Immunol. 154: 33–46.

  • Butscher WG, Powers C, Olive M, Vinson C and Gardner K. . 1998 J. Biol. Chem. 273: 552–560.

  • Chenchik A, Chen S, Makhanov M and Sievert P. . 1998 CLONTECHniques XIII: 16–17.

  • Copeland KF, Haaksma AG, Goudsmit J, Krammer PH and Heeney JL. . 1994 AIDS Res. Hum. Retroviruses 10: 1259–1268.

  • Crepieux P, Kwon H, Leclerc N, Spencer W, Richard S, Lin R and Hiscott J. . 1997 Mol. Cell. Biol. 17: 7375–7385.

  • Cross SL, Feinberg MB, Wolf JB, Holbrook NJ, Wong-Staal F and Leonard WJ. . 1987 Cell 49: 47–56.

  • de Waal Malefyt R, Yssel H, Spits H, de Vries JE, Sancho J, Terhorst C and Alarcon B. . 1990 J. Immunol. 145: 2297–2303.

  • Deveraux QL, Takahashi R, Salvesen GS and Reed JC. . 1997 Nature 388: 300–304.

  • Dick T, Ray K, Salz HK and Chia W. . 1996 Mol. Cell. Biol. 16: 1966–1977.

  • Dorman DM, Wilson DB, Bruns GAP and Orkin SH. . 1992 J. Biol. Chem. 267: 1279–1285.

  • Eischen CM, Williams BL, Zhang W, Samelson LE, Lynch DH, Abraham RT and Leibson PJ. . 1997 J. Immunol. 159: 1135–1139.

  • Feuer G and Chen ISY. . 1992 Biochim. Biophys. Acta 1114: 223–233.

  • Foletta VC, Segal DH and Cohen DR. . 1998 J. Leukocyte Biol. 63: 139–152.

  • Fujii J, Myint T, Okado A, Kaneto H and Taniguchi N. . 1996 Nephrology, Dialysis, Transplantation 11: 34–40.

  • Fujii M, Sassone-Corsi P and Verma IM. . 1988 Proc. Natl. Acad. Sci. USA 85: 8526–8523.

  • Gajewski TF and Thompson CB. . 1996 Cell 87: 589–592.

  • Gonzalez-Garcia A, R-Borlado L, Leonardo E, Mérida I, Martinez-A, C and Carrera AC. . 1997 J. Immunol. 158: 4104–4112.

  • Green PL and Chen ISY. . 1990 FASEB J. 4: 169–175.

  • Gruss J-J and Dower SK. . 1995 Blood 85: 3378–3404.

  • Guenal I, Sidoti-de Fraisse C, Gaumer S and Mignotte B. . 1997 Oncogene 15: 347–360.

  • Hetts SW. . 1998 JAMA 279: 300–307.

  • Hintzen RQ, de Jong R, Lens SMA and van Lier RAW. . 1994 Immunol. Today 15: 307–311.

  • Imura A, Hori T, Imada K, Ishikawa T, Tanaka Y, Maeda M, Imamura S and Uchiyama T. . 1996 J. Exp. Med. 183: 2185–2195.

  • Inoue J, Seiki M, Taniguchi T, Tsuru S and Yoshida M. . 1986 EMBO J. 5: 2883–2888.

  • Jänicke RU, Lin XY, Lee FHH and Porter AG. . 1996 Mol. Cell. Biol. 16: 5245–5253.

  • Jeang K-T, Widen SG, Semmes OJ and Wilson SH. . 1990 Science 247: 1082–1084.

  • Kashanchi F, Duvall JF, Dittmer J, Mireskandari A, Reid RL, Gitlin SD and Brady JN. . 1994 J. Virol. 68: 561–565.

  • Kawai T, Matsumoto M, Takeda K, Sanjo H and Akira S. . 1998 Mol. Cell. Biol. 18: 1642–1651.

  • Kishi S, Saijyo S, Arai M, Karasawa S, Ueda S, Kannagi M, Iwakura Y, Fujii M and Yonehara S. . 1997 J. Exp. Med. 186: 57–64.

  • Koeffler HP, Chen IS and Golde DW. . 1984 Blood 64: 482–490.

  • Koni PA, Sacca R, Lawton P, Browning JL, Ruddle NH and Flavell RA. . 1997 Immunity 6: 491–500.

  • Lemasson I, Robert-Hebmann V, Hamaia S, Duc Dodon M, Gazzolo L and Devaux C. . 1997 J. Virol. 71: 1975–1983.

  • Li C-C, Ruscetti FW, Rice NR, Chen E, Yang N-S, Mikovits J and Longo DL. . 1993 J. Virol. 67: 4205–4213.

  • Lynch DH, Ramsdell F and Alderson MR. . 1995 Immunol. Today 16: 569–574.

  • Maruyama M, Shibuya H, Harada H, Hatakeyama M, Seiki M, Fujita T, Inoue JI, Yoshida M and Taniguchi T. . 1987 Cell 48: 343–350.

  • Mehlen P, Mehlen A, Godet J and Arrigo AP. . 1997 J. Biol. Chem. 272: 31657–31665.

  • Mehlen P, Schulze-Osthoff K and Arrigo AP. . 1996 J. Biol. Chem. 271: 16510–16514.

  • Mena MA, Khan U, Togasaki DM, Sulzer D, Epstein CJ and Przedborski S. . 1997 J. Neurochem. 69: 21–33.

  • Merl S, Kloster B, Moore J, Hubbell C, Tomar R, Davey F, Kalinowski D, Planas A, Ehrlich G and Clark D. . 1984 Blood 64: 967–974.

  • Migita K, Eguchi K, Kawabe Y and Nagataki S. . 1995 Immunology 85: 550–555.

  • Miura K, Titani K, Kurosawa Y and Kanai Y. . 1992 Biochem. Biophys. Res. Commun. 187: 375–380.

  • Miura S, Ohtani K, Numata N, Niki M, Ohbo K, Ina Y, Gojobori T, Tanaka Y, Tozawa H, Nakamura M and Sugamura K. . 1991 Mol. Cell. Biol. 11: 1313–1325.

  • Miyoshi I, Kubonishi I, Yoshimoto S and Shiraishi Y. . 1981 Gann 72: 978–981.

  • Muzio M, Chinnaiyan AM, Kischkel FC, O'Rourke K, Shevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, Mann M, Krammer PH, Peter ME and Dixit VM. . 1996 Cell 85: 817–827.

  • Nagata K, Ohtani K, Nakamura M and Sugamura K. . 1989 J. Virol. 63: 3220–3226.

  • Ohga T, Koike K, Ono M, Makino Y, Itagaki Y, Tanimoto M, Kuwano M and Kohno K. . 1996 Cancer Res. 56: 4224–4228.

  • Ohtani K, Tsujimoto A, Tsukahara T, Numata N, Miura S, Sugamura K and Nakamura M. . 1998 J. Biol. Chem. 273: 14119–14129.

  • Oltvai ZN, Millman CL and Korsmeyer SJ. . 1993 Cell 74: 609–619.

  • Persaud D, Munoz JL, Tarsis SL, Parks ES and Parks WP. . 1995 J. Virol. 69: 6297–6303.

  • Petricoin EF, Ito S, Williams BL, Audet S, Stancato LF, Gamero A, Clouse K, Grimley P, Weiss A, Beeler J, Finbloom DS, Shores EW, Abraham R and Larner AC. . 1997 Nature 390: 629–632.

  • Poiesz BF, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD and Gallo RC. . 1980 Proc. Natl. Acad. Sci. USA 77: 7415–7419.

  • Prosperi MT, Ferbus D, Karczinski I and Goubin G. . 1993 J. Biol. Chem. 268: 11050–11056.

  • Rothe M, Pan M-G, Henzel WJ, Ayres TM and Goeddel DV. . 1995 Cell 83: 1243–1252.

  • Roy N, Deveraux QL, Takahashi R, Salvesen GS and Reed JC. . 1997 EMBO J. 16: 6914–6925.

  • Saggioro D, Wang JM, Sironi M, Luini W, Mantovani A and Chieco-Bianchi L. . 1991 AIDS Res. Hum. Retroviruses 7: 571–577.

  • Sauri H, Butterfield L, Kim A and Shau H. . 1995 Biochem. Biophys. Res. Commun. 208: 964–969.

  • Siekevitz M, Feinberg MB, Holbrook N, Wong-Staal F and Greene WC. . 1987 Proc. Natl. Acad. Sci. USA 84: 5389–5393.

  • Smith MR and Greene WC. . 1991 J. Clin. Invest. 87: 761–766.

  • Sodroski J. . 1992 Biochim. Biophys. Acta. 1114: 19–29.

  • Sugimoto A, Hozak RR, Nakashima T, Nishimoto T and Rothman JH. . 1995 EMBO J. 14: 4434–4441.

  • Tsujimoto A, Nyunoya H, Morita T, Sato T and Shimotohno K. . 1991 J. Virol. 65: 1420–1426.

  • Tsushima H, Urata Y, Miyazaki Y, Fuchigami K, Kuriyama K, Kondo T and Tomonaga M. . 1997 Cell Growth Differ. 8: 1317–1328.

  • Uchiyama T. . 1997 Annu. Rev. Immunol. 15: 15–37.

  • Uittenbogaard MN, Giebler HA, Reisman D and Nyborg JK. . 1995 J. Biol. Chem. 270: 28503–28506.

  • Uren AG, Pakusch M, Hawkins CJ, Puls KL and Vaux DL. . 1996 Proc. Natl. Acad. Sci. USA 93: 4974–4978.

  • Van Antwerp D, Martin SJ, Kafri T, Green DR and Verma IM. . 1996 Science 274: 787–789.

  • Van Snick J, Houssiau F, Proost P, Van Damme J and Renauld JC. . 1996 J. Immunol. 157: 2570–2576.

  • Vaux DL, Cory S and Adams JM. . 1988 Nature 335: 440–442.

  • Wang C-Y, Mayo MW and Baldwin AS Jr. . 1996 Science 274: 784–787.

  • Ware CF, VanArsdale S and VanArsdale TL. . 1996 J. Cell. Biochem. 60: 47–55.

  • Weiss A. . 1993 T lymphocyte activation. In: Fundamental Immunology. WE. Paul (ed.). New York: Raven Press Ltd. pp. 467–504.

    Google Scholar 

  • White E. . 1996 Genes & Dev. 10: 1–15.

  • Yamamoto M, Ko LJ, Leonard MW, Beug H and Orkin SH. . 1990 Genes Dev. 4: 1650–1662.

  • Yin C, Knudson CM, Korsmeyer SJ and Van Dyke T. . 1997 Nature 385: 637–640.

  • Yoshida M. . 1995 J. Cancer Res. Clin. Oncol. 121: 521–528.

  • Yoshida M, Miyoshi I and Hinuma Y. . 1982 Proc. Natl. Acad. Sci. USA 79: 2031–2035.

Download references

Acknowledgements

This study was supported by Public Health Service grant 1 R01 CA68471-03 (to S-CS). EWH is supported by an NIH predoctoral training grant; S-CS is a scholar of the American Society for Hematology.

Author information

Author notes

  1. LiFeng Good

    Present address: Magainin Pharmaceuticals Inc., 5110 Campus Drive, Plymouth Meeting, PA, 19462, USA

Authors and Affiliations

  1. Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, 17033, Pennsylvania, USA

    Edward W Harhaj, LiFeng Good, Gutian Xiao & Shao-Cong Sun

Authors
  1. Edward W Harhaj
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. LiFeng Good
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gutian Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shao-Cong Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Harhaj, E., Good, L., Xiao, G. et al. Gene expression profiles in HTLV-I-immortalized T cells: deregulated expression of genes involved in apoptosis regulation. Oncogene 18, 1341–1349 (1999). https://doi.org/10.1038/sj.onc.1202405

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1202405

Keywords

This article is cited by

Search

Advanced search

Quick links