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Serial analysis of gene expression in renal carcinoma cells reveals VHL-dependent sensitivity to TNFα cytotoxicity

Oncogene volume 21, pages 929–936 (2002)Cite this article

Abstract

We have used serial analysis of gene expression (SAGE) to investigate the influence of the von Hippel-Lindau (VHL) gene on global gene expression profiles. SAGE libraries were prepared from renal cell carcinoma (RCC) lines that either lack (parental) or express wild-type VHL (wtVHL). Comparison of these libraries revealed some differentially expressed genes (Glut-1, for example) that were known to be influenced by VHL, but the majority of genes had not previously been reported to be affected by the cell's VHL status. The identification of several genes involved in TNFα-mediated events prompted us to compare the sensitivity of cells with different VHL status in TNFα cytotoxicity assays. Strikingly, VHL-deficient cells were much more resistant to the toxic influence of TNFα. We propose that VHL-dependent sensitization of RCC cells to TNFα-mediated killing may contribute to VHL's growth suppressive function.

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Abbreviations

CHX:

cycloheximide

RT–PCR:

reverse-transcription-polymerase chain reaction

SAGE:

serial analysis of gene expression

TNFα:

tumor necrosis factor α

VEGF:

vascular endothelial growth factor

VHL:

von Hippel-Lindau

References

  • Arlt A, Grobe O, Sieke A, Kruse M-L, Folsch UR, Schmidt WE, Schafer H . 2001 Oncogene 20: 69–76

  • Chu K, Niu X, Williams LT . 1995 Proc. Natl. Acad. Sci. USA 92: 11894–11898

  • Duan DR, Pause A, Burgess W, Aso T, Chen DYT, Garrett KP, Conaway RC, Conaway JW, Linehan WM, Klausner RD . 1995 Science 269: 1402–1406

  • Fajardo LF, Kwan HH, Kowalski J, Prionas SD, Allison AC . 1992 Amer. J. Pathol. 140: 539–544

  • Feng X, Gaeta ML, Madge LA, Yang J-H, Bradley JR, Pober JS . 2001 J. Biol. Chem. 276: 8341–8349

  • Gnarra JR, Zhou S, Merrill MJ, Wagner JR, Krumm A, Papavassiliou E, Oldfield EH, Klausner RD, Linehan WM . 1996 Proc. Natl. Acad. Sci. USA 93: 10589–10594

  • Gorospe M, Egan JM, Zbar B, Lerman M, Geil L, Kuzmin I, Holbrook NJ . 1999 Mol. Cell. Biol. 19: 1289–1300

  • Gorospe M, Holbrook NJ . 1996 Cancer Res. 56: 475–479

  • Hough C, Sherman-Baust CA, Pizer ES, Montz FJ, Im DD, Rosensheim NB, Cho KR, Riggins GJ, Morin PJ . 2000 Cancer Res. 60: 6281–6287

  • Iliopoulos O, Levy AP, Jiang C, Kaelin Jr WG, Goldberg MA . 1996 Proc. Natl. Acad. Sci. USA 93: 10595–10599

  • Ivan M, Kaelin WG . 2001 Curr. Op. Gen. Dev. 11: 27–34

  • Kroll SL, Paulding WR, Schnell PO, Barton MC, Conaway JW, Conaway RC, Czyzyk-Krzeska MF . 1999 J. Biol. Chem. 274: 30109–30114

  • Madden SL, Galella EA, Zhu J, Bertelsen AH, Beaudry GA . 1997 Oncogene 15: 1079–1085

  • Maxwell PH, Wiesener MS, Chang G-W, Clifford SC, Vaux EC, Cockman ME, Wykoff CC, Pugh CW, Maher ER, Ratcliffe PJ . 1999 Nature 399: 271–275

  • Moch H, Schraml P, Bubendorf L, Mirlacher M, Kononen J, Gasser T, Mihatsch MJ, Kallioniemi OP, Sauter G . 1999 Am. J. Pathol. 154: 981–986

  • Moutet M, d'Alessio P, Malette P, Devaux V, Chaudiere J . 1998 Free Radic. Biol. Med. 25: 270–281

  • Mukhopadhyay D, Knebelmann B, Cohen HT, Ananth S, Sukhatme VP . 1997 Mol. Cell. Biol. 17: 5629–5639

  • Ohh M, Park CW, Ivan M, Hoffman MA, Kim T-Y, Huang LE, Chau V, Kaelin WG . 2000 J. Biol. Chem. 275: 25733–25741

  • Rae FK, Stephenson S-A, Nicol DL, Clements JA . 2000 Int. J. Cancer 88: 726–732

  • Sato K, Terada K, Sugiyama T, Takahashi S, Saito M, Moriyama M, Kakinuma H, Suzuki Y, Kato M, Kato T, Tohoku J . 1994 Exp. Med. 173: 355–360

  • Song HY, Dunbar JD, Zhang YX, Guo D, Donner DB . 1995 J. Biol. Chem. 270: 3574–3581

  • Spyridopoulos I, Brogi E, Kearney M, Sullivan AB, Cetrulo C, Isner JM, Losordo DW . 1997 J. Mol. Cell. Cardiol. 29: 1321–1330

  • Velculescu VE, Zhang L, Vogelstein B, Kinzler KW . 1995 Science 270: 484–487

  • Wizigmann-Voos S, Breier G, Risau W, Plate K . 1995 Cancer Res. 55: 1358–1364

  • Wu MX, Ao Z, Prasad KV, Wu R, Schlossman SF . 1998 Science 281: 998–1001

  • Wykoff CC, Pugh CW, Maxwell PH, Harris AL, Ratcliffe PJ . 2000 Oncogene 19: 6297–6305

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Acknowledgements

We are grateful to J Gnarra for providing the UOK-121 cells, O Iliopoulos and WG Kaelin for providing the 786–0 cells, and MI Lerman and B Zbar for providing the UMRC6 cells. We thank NJ Holbrook, S Shack, CA Sherman-Baust and RD Klausner for helpful discussions.

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Authors and Affiliations

  1. Laboratory of Cellular and Molecular Biology, National Institute on Aging - IRP, National Institutes of Health, Baltimore, 21224, Maryland, MD, USA

    M Craig Caldwell, Colleen Hough, Stefanie Fürer, Patrice J Morin & Myriam Gorospe

  2. Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, 20892, Maryland, MD, USA

    W Marston Linehan

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  1. M Craig Caldwell
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  2. Colleen Hough
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  3. Stefanie Fürer
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  4. W Marston Linehan
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  5. Patrice J Morin
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  6. Myriam Gorospe
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Correspondence to Myriam Gorospe.

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Caldwell, M., Hough, C., Fürer, S. et al. Serial analysis of gene expression in renal carcinoma cells reveals VHL-dependent sensitivity to TNFα cytotoxicity. Oncogene 21, 929–936 (2002). https://doi.org/10.1038/sj.onc.1205140

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