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  • Original Paper
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Expression profiling of glucocorticoid-treated T-ALL cell lines: rapid repression of multiple genes involved in RNA-, protein- and nucleotide synthesis

Oncogene volume 20, pages 4324–4336 (2001)Cite this article

Abstract

To arrive at a better understanding of the effects of the glucocorticoid component of chemotherap#y protocols on lymphocytic leukemia cells, we analysed early responses of T-lymphocytic leukemia cell lines Jurkat and CEM-C7, both of which undergo apoptosis in response to dexamethasone, via gene chips. Among genes identified as repressed, a notable cluster seemed to be of importance for the processes of transcription, mRNA splicing and protein synthesis. Consequently, we assessed time-resolved uptake of uridine and methionine to monitor RNA and protein synthesis, along with parameters quantifying apoptosis. Repression of uptake to about 65% of that in untreated cells preceded the first sign of apoptosis by several hours in both cell lines. In addition to this general repression of RNA and protein synthesis, several genes were found to be regulated that may contribute to synergistic action of glucocorticoids with other components of frequently used chemotherapy protocols such as antimetabolites, methotrexate and alkylating agents.

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References

  • Albers MW, Brown EJ, Tanaka A, Williams RT, Hall FL, Schreiber SL . 1993 Ann. NY Acad. Sci. 696: 54–62

  • Alizadeh AA, Eisen MB, Davis RE, et al. 2000 Nature 403: 503–511

  • Altmeyer A, Simmons RC, Krajewski S, Reed JC, Bornkamm GW, Chen-Kiang S . 1997 Immunity 7: 667–677

  • Antakly T, Thompson EB, O’Donnell D . 1989 Cancer Res. 49: 2230s–2234s

  • Ashraf J, Kunapuli S, Chilton D, Thompson EB . 1991 J. Steroid Biochem. Mol. Biol. 38: 561–568

  • Auphan N, DiDonato JA, Rosette C, Helmberg A, Karin M . 1995 Science 270: 286–290

  • Baxter JD . 2000 Adv. Intern. Med. 45: 317–349

  • Baxter JD, Harris AW, Tomkins GM, Cohn M . 1971 Science 171: 189–191

  • Beato M, Herrlich P, Schütz G . 1995 Cell 83: 851–857

  • Bortner CD, Cidlowski JA . 1999 J. Biol. Chem. 274: 21953–21962

  • Brown EJ, Albers MW, Shin TB, Ichikawa K, Keith CT, Lane WS, Schreiber SL . 1994 Nature 369: 756–758

  • Brown EJ, Schreiber SL . 1996 Cell 86: 517–520

  • Burnstein KL, Jewell CM, Sar M, Cidlowski JA . 1994 Mol. Endocrinol. 8: 1764–1773

  • Caron-Leslie LA, Evans RB, Cidlowski JA . 1994 FASEB J. 8: 639–645

  • Chabner BA, Allegra CJ, Curt GA, Calabresi P . 1996 Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gilman AG (eds.), The Pharmacological Basis of Therapeutics, 9th ed McGraw-Hill: New York pp. 1233–1271

  • Chapman MS, Askew DJ, Kuscuoglu U, Miesfeld RL . 1996 Mol. Endocrinol. 10: 967–978

  • Chaudhary N, McMahon C, Blobel G . 1991 Proc. Natl. Acad. Sci. USA 88: 8189–8193

  • Chen MJ, Shimada T, Moulton AD, Cline A, Humphries RK, Maizel J, Nienhuis AW . 1984 J. Biol. Chem. 259: 3933–3943

  • Chen Q, Baird SD, Mahadevan M, Besner-Johnston A, Farahani R, Xuan J, Kang X, Lefebvre C, Ikeda JE, Korneluk RG, MacKenzie AE . 1998 Genomics 48: 121–127

  • Cruzen ME, Arfin SM . 1994 DNA Seq 4: 243–248

  • Dayan A, Bertrand R, Beauchemin M, Chahla D, Mamo A, Filion M, Skup D, Massie B, Jolivet J . 1995 Gene 165: 307–311

  • Denton RR, Eisen LP, Elsasser MS, Harmon JM . 1993 Endocrinology 133: 248–256

  • Eisen LP, Elsasser MS, Harmon JM . 1988 J. Biol. Chem. 263: 12044–12048

  • Elisei R, Weightman D, Kendall-Taylor P, Vassart G, Ludgate M . 1993 J. Endocrinol. Invest. 16: 533–540

  • Fischer U, Liu Q, Dreyfuss G . 1997 Cell 90: 1023–1029

  • Foley GE, Lazarus H . 1967 Biochem. Pharmacol. 16: 659–674

  • Geley S, Fiegl M, Hartmann BL, Kofler R . 1996a Rev. Physiol. Biochem. Pharmacol. 128: 1–97

  • Geley S, Hartmann BL, Hala M, Strasser-Wozak EM, Kapelari K, Kofler R . 1996b Cancer Res. 56: 5033–5038

  • Gipp JJ, Bailey HH, Mulcahy RT . 1995 Biochem. Biophys. Res. Commun. 206: 584–589

  • Godowski PJ, Sakai DD, Yamamoto KR . 1989 DNA-Protein Interactions in Transcription, UCLA Symposia on Molecular and Cellular Biology, New Series, vol. 95. JD Gralla, Alan R, Liss (eds). New York pp. 197–210

    Google Scholar 

  • Gomi M, Moriwaki K, Katagiri S, Kurata Y, Thompson EB . 1990 Cancer Res. 50: 1873–1878

  • Göttlicher M, Heck S, Herrlich P . 1998 J. Mol. Med. 76: 480–489

  • Harmon JM, Norman MR, Fowlkes BJ, Thompson EB . 1979 J. Cell Physiol. 98: 267–278

  • Hartmann BL, Geley S, Loffler M, Hattmannstorfer R, Strasser-Wozak EM, Auer B, Kofler R . 1999 Oncogene 18: 713–719

  • Heck S, Bender K, Kullmann M, Göttlicher M, Herrlich P, Cato AC . 1997 EMBO J. 16: 4698–4707

  • Helmberg A, Auphan N, Caelles C, Karin M . 1995 EMBO J. 14: 452–460

  • Helmberg A, Fässler R, Geley S, Jöhrer K, Kroemer G, Böck G, Kofler R . 1990 J. Immunol. 145: 4332–4337

  • Honore B, Rasmussen HH, Vorum H, Dejgaard K, Liu X, Gromov P, Madsen P, Gesser B, Tommerup N, Celis JE . 1995 J. Biol. Chem. 270: 28780–28789

  • Hortsch M, Labeit S, Meyer DI . 1988 Nucleic Acids Res. 16: 361–362

  • Hsieh SL, Campbell RD . 1991 Biochem J. 278: 809–816

  • Huang SH, Tang A, Drisco B, Zhang SQ, Seeger R, Li C, Jong A . 1994 DNA Cell Biol. 13: 461–471

  • Iwahana H, Fujimura M, Ii S, Kondo M, Moritani M, Takahashi Y, Yamaoka T, Yoshimoto K, Itakura M . 1996 Biochem. Biophys. Res. Commun. 219: 249–255

  • Karin M . 1998 Cell 93: 487–490

  • Kullmann M, Schneikert J, Moll J, Heck S, Zeiner M, Gehring U, Cato AC . 1998 J. Biol. Chem. 273: 14620–14625

  • Lipshutz RJ, Fodor SPA, Gingeras TR, Lockhart DJ . 1999 Nature Genet. 21: 1 Suppl 20–24

  • Marchetti P, Castedo M, Susin SA, Zamzami N, Hirsch T, Macho A, Haeffner A, Hirsch F, Geuskens M, Kroemer G . 1996 J. Exp. Med. 184: 1155–1160

  • Mita K, Tsuji H, Morimyo M, Takahashi E, Nenoi M, Ichimura S, Yamauchi M, Hongo E, Hayashi A . 1995 Gene 159: 285–286

  • Moulding DA, Quayle JA, Hart CA, Edwards SW . 1998 Blood 92: 2495–2502

  • Nicoletti I, Migliorati G, Pagliacci MC, Grignani F, Riccardi C . 1991 J. Immunol. Meth. 139: 271–279

  • Owens-Grillo JK, Hoffmann K, Hutchison KA, Yem AW, Deibel Jr MR, Handschumacher RE, Pratt WB . 1995 J. Biol. Chem. 270: 20479–20484

  • Poot M, Zhang YZ, Kramer JA, Wells KS, Jones LJ, Hanzel DK, Lugade AG, Singer VL, Haugland RP . 1996 J. Histochem. Cytochem. 44: 1363–1372

  • Ramdas J, Liu W, Harmon JM . 1999 Cancer Res. 59: 1378–1385

  • Reichardt HM, Kaestner KH, Tuckermann J, Kretz O, Wessely O, Bock R, Gass P, Schmid W, Herrlich P, Angel P, Schütz G . 1998 Cell 93: 531–541

  • Reichardt HM, Schütz G . 1998 Mol. Cell. Endocrinol. 146: 1–6

  • Scheinman RI, Cogswell PC, Lofquist AK, Baldwin Jr AS . 1995 Science 270: 283–286

  • Schimmer BP, Parker KL . 1996 Hardman JG, Limbird LE, Molinoff PB, Ruddon RW and Gilman AG . (eds). The Pharmacological Basis of Therapeutics, 9th edn McGraw-Hill: New York pp. 1465–1481

    Google Scholar 

  • Schrank B, Gotz R, Gunnersen JM, Ure JM, Toyka KV, Smith AG, Sendtner M . 1997 Proc. Natl. Acad. Sci. USA 94: 9920–9925

  • Seelig HP, Moosbrugger I, Ehrfeld H, Fink T, Renz M, Genth E . 1995 Arthritis Rheum. 38: 1389–1399

  • Sibley CH, Tomkins GM . 1974 Cell 2: 213–220

  • Sillekens PT, Beijer RP, Habets WJ, van Venrooij WJ . 1988 Nucleic Acids Res. 16: 8307–8321

  • Silverstein AM, Galigniana MD, Chen MS, Owens-Grillo JK, Chinkers M, Pratt WB . 1997 J. Biol. Chem. 272: 16224–16230

  • Silverstein AM, Galigniana MD, Kanelakis KC, Radanyi C, Renoir JM, Pratt WB . 1999 J. Biol. Chem. 274: 36980–36986

  • Tai PK, Albers MW, Chang H, Faber LE, Schreiber SL . 1992 Science 256: 1315–1318

  • Thompson EB . 1999 Trends Endocrinol. Metab. 10: 353–358

  • Thulasi R, Harbour DV, Thompson EB . 1993 J. Biol. Chem. 268: 18306–18312

  • Tonko M, Ausserlechner MJ, Bernhard D, Helmberg A, Kofler R . 2001 FASEB J. 15: 693–699

  • Tsui FW, Siminovitch L . 1987 Nucleic Acids Res. 15: 3349–3367

  • Wang W, Xue Y, Zhou S, Kuo A, Cairns BR, Crabtree GR . 1996 Genes Dev. 10: 2117–2130

  • Webster JC, Cidlowski JA . 1999 Trends Endocrinol. Metab. 10: 396–402

  • Weinzierl RO, Ruppert S, Dynlacht BD, Tanese N, Tjian R . 1993 EMBO J. 12: 5303–5309

  • Yoon JB, Roeder RG . 1996 Mol. Cell. Biol. 16: 1–9

  • Zeiner M, Gebauer M, Gehring U . 1997 EMBO J. 16: 5483–5490

  • Zeiner M, Gehring U . 1995 Proc. Natl. Acad. Sci. USA 92: 11465–11469

  • Zeiner M, Niyaz Y, Gehring U . 1999 Proc. Natl. Acad. Sci. USA 96: 10194–10199

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Acknowledgements

We would like to thank Dr G Böck for help with flow cytometry, Yvonne Burki for expert assistance with gene chip hybridization, and Drs Georg Wick, Roswitha Sgonc, Stephan Geley, Michael J Ausserlechner and Wolfgang Doppler for critical reading, and MK Occhipinti for editing the manuscript. This work was supported by grants P11306 and F204 from the Austrian Science Fund.

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Authors and Affiliations

  1. Institute of Pathophysiology, University of Innsbruck, Medical School, Innsbruck, A 6020, Austria

    Petra Obexer, Reinhard Kofler & Arno Helmberg

  2. Roche Genetics, F. Hoffmann-La Roche Ltd., Basel, 4070, CH, Switzerland

    Ulrich Certa

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  1. Petra Obexer
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  2. Ulrich Certa
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  3. Reinhard Kofler
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  4. Arno Helmberg
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Correspondence to Arno Helmberg.

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Obexer, P., Certa, U., Kofler, R. et al. Expression profiling of glucocorticoid-treated T-ALL cell lines: rapid repression of multiple genes involved in RNA-, protein- and nucleotide synthesis. Oncogene 20, 4324–4336 (2001). https://doi.org/10.1038/sj.onc.1204573

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