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Comparative microarray analysis of gene expression during apoptosis-induction by growth factor deprivation or protein kinase C inhibition

Oncogene volume 19, pages 5073–5082 (2000)Cite this article

Abstract

The transcriptional response of mouse pro-B cells to two different apoptotic stimuli was investigated. First, interleukin-3 (IL-3) deprivation was used to trigger programmed cell death in IL-3 dependent FL5.12 cells. Alternatively, cells were treated with the protein kinase C (PKC) inhibitor staurosporine. The temporal pattern of gene expression was followed with cDNA microarrays, covering over 8700 different mouse cDNA sequences corresponding to approximately 7900 unique genes. Messenger RNA levels of 315 genes were found to be regulated by more than twofold upon IL-3 removal, while 125 genes reacted to staurosporine treatment. Cross-comparison revealed an intersection of 34 genes similarly regulated in both pathways and thus representing candidates for common apoptosis regulators. For many expressed sequence tags (ESTs) our data suggest for the first time functions in the control of apoptosis, stress response or the cell cycle. IL-3 removal led to the repression of genes required for proliferation and to the induction of genes, linked to apoptotic and signaling pathways. Staurosporine caused predominantly activation of genes, some of which had previously been described to be involved in inflammation. Our findings indicate that cellular responses to both apoptotic stimuli influence various physiological pathways which had not previously been known to be linked.

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References

  • Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J and Greenberg ME. . 1999 Cell 96: 857–868.

  • Bertrand R, Solary E, O'Connor P, Kohn KW and Pommier Y. . 1994 Exp. Cell. Res. 211: 314–321.

  • Besancon F, Atfi A, Gespach C, Cayre YE and Bourgeade MF. . 1998 Proc. Natl. Acad. Sci. USA 95: 8081–8086.

  • Blandino G, Scardigli R, Rizzo MG, Crescenzi M, Soddu S and Sacchi A. . 1995 Oncogene 104: 731–737.

  • Cardone MH, Roy N, Stennike HR, Salvesen GS, Franke TF, Stanbridge E, Frisch S and Reed JC. . 1998 Science 282: 1318–1321.

  • Chowdhury K, Rohdewohld H and Gruss P. . 1988 Nucl. Acids Res. 16: 9995–10011.

  • Chubatsu LS and Meneghini R. . 1993 Biochem. J. 291: 193–198.

  • Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y and Greenberg ME. . 1997 Cell 91: 231–241.

  • Denhardt DT and Noda M. . 1998 J. Cell Biochem. Suppl 30–31: 92–102.

  • De Valck D, Jin DY, Heyninck K, Van de Craen M, Contreras R, Fiers W, Jeang KT and Beyaert R. . 1999 Oncogene 18: 4182–4190.

  • Dupressoir A, Barbot W, Loireau MP and Heidmann T. . 1999 J. Biol. Chem. 274: 31068–31075.

  • Ellis HM and Horvitz HR. . 1986 Cell 44: 817–829.

  • Emoto Y, Manome Y, Meinhardt G, Kisaki H, Kharbanda S, Robertson M, Ghayur T, Wong WW, Kamen R, Weichselbaum R, et al. 1995 EMBO J. 14: 6148–6156.

  • Galvin JP, Spaeny-Dekking LH, Wang B, Seth P, Hack CE and Froelich CJ. . 1999 J. Immunol. 162: 5345–5350.

  • Ghayur T, Hugunin M, Talanian RV, Ratnofsky S, Quinlan C, Emoto Y, Pandey P, Datta R, Huang Y, Kharbanda S, Allen H, Kamen R, Wong W and Kufe D. . 1996 J. Exp. Med. 184: 2399–2404.

  • Germain M, Affar EB, D'Amours D, Dixit VM, Salvesen GS and Poirier GG. . 1999 J. Biol. Chem. 274: 28379–28384.

  • Gottlieb E and Oren M. . 1998 EMBO J. 17: 3587–3596.

  • Grummt I. . 1999 Prog. Nucleic Acid Res. Mol. Biol. 62: 109–154.

  • Gupta AK, Fisher GJ, Elder JT, Nickoloff BJ and Voorhees JJ. . 1988 J. Invest. Dermatol. 91: 486–491.

  • Hamilton GS and Steiner JP. . 1998 Med. Chem. 41: 5119–5143.

  • Hartigan JA. . 1975 Clustering Algorithms. John Wiley and Sons: New York.

    Google Scholar 

  • Hesselgesser J, Taub D, Baskar P, Greenberg M, Hoxie J, Kolson DL and Horuk R. . 1998 Curr. Biol. 8: 595–598.

  • Heyworth C, Gale K, Dexter M, May G and Enver TA. . 1999 Genes Dev. 13: 1847–1860.

  • Hisaeda H, Sakai T, Ishikawa H, Maekawa Y, Yasutomo K, Good RA and Himeno K. . 1997 J. Immunol. 159: 2375–2381.

  • Jiang S, Cai J, Wallace DC and Jones DP. . 1999 J. Biol. Chem. 274: 29905–29911.

  • Inglis JD, Lee M, Davidson DR and Hill RE. . 1991 Gene 106: 213–220.

  • Inukai T, Inoue A, Kurosawa H, Goi K, Shinjyo T, Ozawa K, Mao M, Inaba T and Look AT. . 1999 Mol. Cell. 4: 343–352.

  • Ikushima S, Inukai T, Inaba T, Nimer SD, Cleveland JL and Look AT. . 1997 Proc. Natl. Acad. Sci. USA 94: 2609–2614.

  • Kasibhatla S, Brunner T, Genestier L, Echeverri F, Mahboubi A and Green DR. . 1998 Cell 1: 543–551.

  • Kataoka M, Yoshiyama K, Matsuura K, Hijiya N, Higuchi Y and Yamamoto S. . 1997 J. Biol. Chem. 272: 18209–18215.

  • Kerkhoff C, Klempt M and Sorg C. . 1998 Biochim. Biophys. Acta 1448: 200–211.

  • Khanna KK and Lavin MF. . 1993 Oncogene 8: 3307–3312.

  • Kimura H, Takizawa N, Nozaki N and Sugimoto K. . 1995 Nucl. Acids Res. 23: 2097–2104.

  • Kume K and Shimizu T. . 1997 Biochem. Biophys. Res. Commun. 237: 663–666.

  • La Rosa FA, Pierce JW and Sonenshein GE. . 1994 Mol. Cell. Biol. 14: 1039–1044.

  • Lentsch AB and Ward PA. . 1999 Clin. Chem. Lab. Med. 373: 205–208.

  • Li F and Altieri DC. . 1999 Cancer Res. 59: 3143–3151.

  • Lotscher E and Allison JP. . 1990 Nucl. Acids Res. 18: 7153.

  • Martin SJ, Lennon SV, Bonham AM and Cotter TG. . 1990 J. Immunol. 145: 1859–1867.

  • Matsumoto A, Masuhara M, Mitsui K, Yokouchi M, Ohtsubo M, Misawa H, Miyajima A and Yoshimura A. . 1997 Blood 89: 3148–3154.

  • Michelotti EF, Tomonaga T, Krutzsch H and Levens D. . 1995 J. Biol. Chem. 270: 9494–9499.

  • Mizuki K, Kadomatsu K, Hata K, Ito T, Fan QW, Kage Y, Fukumaki Y, Sakaki Y, Takeshige K and Sumimoto H. . 1998 Eur. J. Biochem. 251: 573–582.

  • Miyashita T and Reed JC. . 1995 Cell 80: 293–299.

  • Moolenaar WH and van Corven EJ. . 1990 Ciba. Found Symp. 150: 99–106.

  • Mui AL, Wakao H, Kinoshita T, Kitamura T and Miyajima A. . 1996 EMBO J. 15: 2425–2433.

  • Oliver FJ, Collins MK and Lopez-Rivas A. . 1996 Biochem. J. 316: 421–425.

  • Oliver FJ, Collins MKL and Lopez-Rivas A. . 1997 J. Biol. Chem. 18: 10624–10630.

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

  • Patarca R, Freeman GJ, Schwartz J, Singh RP, Kong QT, Murphy E, Anderson Y, Sheng FY, Singh P, Johnson KA, Guarnagia SM, Durfee T, Blattner F and Cantor H. . 1988 Proc. Natl. Acad. Sci. USA 85: 2733–2737.

  • Paumen MB, Ishida Y, Muramatsu M, Yamamoto M and Honjo T. . 1997 J. Biol. Chem. 272: 3324–3329.

  • Perillo NL, Marcus ME and Baum LG. . 1998 J. Mol. Med. 76: 402–412.

  • Persons DA, Allay JA, Allay ER, Ashmun RA, Orlic D, Jane SM, Cunningham JM and Nienhuis AW. . 1999 Blood 93: 488–499.

  • Pierrat B, Correia JS, Mary JL, Tomas-Zuber M and Lesslauer W. . 1998 J. Biol. Chem. 273: 29661–29671.

  • Rabinovich GA. . 1999 Cell. Death Differ. 6: 711–721.

  • Reynolds NJ, McCombie SW, Shankar BB, Bishop WR and Fisher GJ. . 1997 Arch. Dermatol. Res. 289: 540–546.

  • Rickers A, Peters N, Badock V, Beyaert R, Vandenabeele P, Dorken B and Bommert K. . 1999 Eur. J. Biochem. 261: 269–274.

  • Rosenfeld ME. . 1998 Semin. Reprod. Endocrinol. 16: 249–261.

  • Rouault JP, Falette N, Guehenneux F, Guillot C, Rimokh R, Wang Q, Berthet C, Moyret-Lalle C, Savatier P, Pain B, Shaw P, Berger R, Samarut J, Magaud JP, Ozturk M, Samarut C and Puisieux A. . 1996 Nat. Genet. 14: 482–486.

  • Rouault JP, Prevot D, Berthet C, Birot AM, Billaud M, Magaud JP and Corbo L. . 1998 J. Biol. Chem. 273: 22563–22569.

  • Scatena M, Almeida M, Chaisson ML, Fausto N, Nicosia RF and Giachelli CM. . 1998 J. Cell. Biol. 141: 1083–1093.

  • Schena M, Shalon D, Davis RW and Brown PO. . 1995 Science 270: 467–470.

  • Schena M, Shalon D, Heller R, Chai A, Brown PO and Davis RW. . 1996 Proc. Natl. Acad. Sci. USA 93: 10614–10619.

  • Simpkins C, Lloyd T, Li S and Balderman S. . 1998 J. Surg. Res. 75: 30–34.

  • Steller H. . 1995 Science 267: 1445–1449.

  • Sun HB, Zhu YX, Yin T, Sledge G and Yang YC. . 1998 Proc. Natl. Acad. Sci. USA 95: 13555–13560.

  • Tanaka Y, Adams DH, Hubscher S, Hirano H, Siebenlist U and Shaw S. . 1993 Nature 361: 79–82.

  • Thompson CB. . 1995 Science 267: 1456–1462.

  • Tsai FY, Keller G, Kuo FC, Weiss M, Chen J, Rosenblatt M, Alt FW and Orkin SH. . 1994 Nature 371: 221–226.

  • Urbanowicz-Kachnowicz I, Baghdassarian N, Nakache C, Gracia D, Mekki Y, Bryon PA and Ffrench M. . 1999 Int. J. Cancer 82: 98–104.

  • Vainberg IE, Lewis SA, Rommelaere H, Ampe C, Vandekerckhove J, Klein HL and Cowan NJ. . 1998 Cell 93: 863–873.

  • Wada J and Kanwar YS. . 1997 J. Biol. Chem. 272: 6078–6086.

  • Wada J, Ota K, Kumar A, Wallner EI and Kanwar YS. . 1997 J. Clin. Invest. 9: 2452–2461.

  • Wu M, Arsura M, Bellas RE, FitzGerald MJ, Lee H, Schauer SL, Sherr DH and Sonenshein GE. . 1996 Mol. Cell. Biol. 16: 5015–5025.

  • Wu Y, Prystowsky MB and Orlofsky A. . 1999 Cytokine 11: 523–530.

  • Xiao YQ, Someya K, Morita H, Takahashi K and Ohuchi K. . 1999 Biochim. Biophys. Acta 1450: 155–163.

  • Yaron A, Hatzubai A, Davis M, Lavon I, Amit S, Manning AM, Andersen JS, Mann M, Mercurio F and Ben-Neriah Y. . 1998 Nature 396: 590–594.

  • Zhang H, Hoang T and Saeed B. . 1996 Prostate 29: 69–76.

  • Zhang H, Brandt R, Heim J and Meyhack B. . 1999 Int. J. Oncol. 14: 113–120.

  • Zhou J and Saba JD. . 1998 Biochem. Biophys. Res. Commun. 242: 502–507.

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Acknowledgements

We thank Marion Kamke, Brigitte Besenreuther, and Rita Grossenbacher for excellent technical assistance.

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Authors and Affiliations

  1. Molecular and Cellular Biology Senior Scientific Expert Laboratory, Novartis Pharma AG, Basel, CH-4002, Switzerland

    Arndt Brachat, Benoit Pierrat & Jutta Heim

  2. Oncology Research, Novartis Pharma AG, Basel, CH-4002, Switzerland

    Adrian Brüngger

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Brachat, A., Pierrat, B., Brüngger, A. et al. Comparative microarray analysis of gene expression during apoptosis-induction by growth factor deprivation or protein kinase C inhibition. Oncogene 19, 5073–5082 (2000). https://doi.org/10.1038/sj.onc.1203882

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