Differential cooperation of oncogenes with p53 and Bax to induce apoptosis in rhabdomyosarcoma

Alan Taylor, Katja Schuster, Pamela P. McKenzie, Linda C. Harris

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Deregulated expression of oncogenes such as MYC and PAX3-FKHR often occurs in rhabdomyosarcomas. MYC can enhance cell proliferation and apoptosis under specific conditions, whereas PAX3-FKHR has only been described as anti-apoptotic. Results: In order to evaluate how MYC and PAX3-FKHR oncogenes influenced p53-mediated apoptosis, rhabdomyosarcoma cells were developed to independently express MYC and PAX3-FKHR cDNAs. Exogenous wild-type p53 expression in MYC transfected cells resulted in apoptosis, whereas there was only a slight effect in those transfected with PAX3-FKHR. Both oncoproteins induced BAX, but BAX induction alone without expression of wild-type p53 was insufficient to induce apoptosis. Data generated from genetically modified MEFs suggested that expression of all three proteins; MYC, BAX and p53, was required for maximal cell death to occur. Conclusion: We conclude that cooperation between p53 and oncoproteins to induce apoptosis is dependent upon the specific oncoprotein expressed and that oncogene-mediated induction of BAX is necessary but insufficient to enhance p53-mediated apoptosis. These data demonstrate a novel relationship between MYC and p53-dependent apoptosis, independent of the ability of MYC to induce p53 that may be important in transformed cells other than rhabdomyosarcoma.

Original languageEnglish (US)
Article number53
JournalMolecular Cancer
Volume5
DOIs
StatePublished - Nov 2 2006
Externally publishedYes

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Rhabdomyosarcoma
Oncogenes
Apoptosis
Oncogene Proteins
Tumor Suppressor Protein p53
Cell Death
Complementary DNA
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Oncology
  • Cancer Research

Cite this

Differential cooperation of oncogenes with p53 and Bax to induce apoptosis in rhabdomyosarcoma. / Taylor, Alan; Schuster, Katja; McKenzie, Pamela P.; Harris, Linda C.

In: Molecular Cancer, Vol. 5, 53, 02.11.2006.

Research output: Contribution to journalArticle

Taylor, Alan ; Schuster, Katja ; McKenzie, Pamela P. ; Harris, Linda C. / Differential cooperation of oncogenes with p53 and Bax to induce apoptosis in rhabdomyosarcoma. In: Molecular Cancer. 2006 ; Vol. 5.
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