The von Hippel-Lindau tumor suppressor gene protects cells from UV-mediated apoptosis

Alan R. Schoenfeld, Tchaiko Parris, Andrew Eisenberger, Eliot J. Davidowitz, Maryely De Leon, Faranaz Talasazan, Prasad Devarajan, Robert D. Burk

Research output: Contribution to journalArticle

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Abstract

The familial cancer syndrome, von Hippel-Lindau (VHL) disease, characterized by a predisposition to renal cell carcinoma and certain other tumor types, is caused by mutational inactivation of the VHL tumor suppressor gene. Loss of VHL gene function is detected also in the vast majority of sporadic renal cell carcinomas. Previous reports have determined a protective role for VHL in response to serum withdrawal and glucose deprivation. In this study, the effect of UV irradiation on VHL-negative and VHL-positive renal carcinoma cells was examined. VHL-negative 786-O renal carcinoma cells underwent apoptosis following UV irradiation. In contrast, reintroduction of wild-type VHL expression protected 786-O cells from UV-mediated cell death. p53 and Bax levels were equivalent in VHL-negative and VHL-positive 786-O cells. Strikingly, cyclin-dependent kinase inhibitors p21 and p27 underwent proteasome-dependent degradation in VHL-negative 786-O cells following UV treatment. However, p21 and p27 protein levels were stable in VHL-positive cells. Also, levels of the anti-apoptotic proteins, Bcl-2 and Bcl-xL were elevated in VHL-positive cells, consistent with the protection from apoptotic stimuli. UV treatment led to increased S phase in VHL-negative, but not VHL-positive cells. Thus, following UV irradiation, diminution of p21 and p27 levels resulted in a hyperproliferative state in VHL-negative cells, leading to apoptosis. These results suggest that loss of VHL function promotes apoptosis and may provide selective pressure toward cells that are able to escape apoptosis, leading to tumorigenesis.

Original languageEnglish (US)
Pages (from-to)5851-5857
Number of pages7
JournalOncogene
Volume19
Issue number51
DOIs
StatePublished - Nov 30 2000

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Tumor Suppressor Genes
Apoptosis
Renal Cell Carcinoma
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinase Inhibitor p27
von Hippel-Lindau Disease
Apoptosis Regulatory Proteins
Proteasome Endopeptidase Complex
S Phase
Neoplasms
Carcinogenesis
Cell Death
Glucose
Therapeutics
Serum
Genes
Proteins

Keywords

  • Apoptosis, UV
  • Renal cell carcinoma
  • VHL
  • Von Hippel-Lindau

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Schoenfeld, A. R., Parris, T., Eisenberger, A., Davidowitz, E. J., De Leon, M., Talasazan, F., ... Burk, R. D. (2000). The von Hippel-Lindau tumor suppressor gene protects cells from UV-mediated apoptosis. Oncogene, 19(51), 5851-5857. https://doi.org/10.1038/sj.onc.1203985

The von Hippel-Lindau tumor suppressor gene protects cells from UV-mediated apoptosis. / Schoenfeld, Alan R.; Parris, Tchaiko; Eisenberger, Andrew; Davidowitz, Eliot J.; De Leon, Maryely; Talasazan, Faranaz; Devarajan, Prasad; Burk, Robert D.

In: Oncogene, Vol. 19, No. 51, 30.11.2000, p. 5851-5857.

Research output: Contribution to journalArticle

Schoenfeld, AR, Parris, T, Eisenberger, A, Davidowitz, EJ, De Leon, M, Talasazan, F, Devarajan, P & Burk, RD 2000, 'The von Hippel-Lindau tumor suppressor gene protects cells from UV-mediated apoptosis', Oncogene, vol. 19, no. 51, pp. 5851-5857. https://doi.org/10.1038/sj.onc.1203985
Schoenfeld AR, Parris T, Eisenberger A, Davidowitz EJ, De Leon M, Talasazan F et al. The von Hippel-Lindau tumor suppressor gene protects cells from UV-mediated apoptosis. Oncogene. 2000 Nov 30;19(51):5851-5857. https://doi.org/10.1038/sj.onc.1203985
Schoenfeld, Alan R. ; Parris, Tchaiko ; Eisenberger, Andrew ; Davidowitz, Eliot J. ; De Leon, Maryely ; Talasazan, Faranaz ; Devarajan, Prasad ; Burk, Robert D. / The von Hippel-Lindau tumor suppressor gene protects cells from UV-mediated apoptosis. In: Oncogene. 2000 ; Vol. 19, No. 51. pp. 5851-5857.
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