Hsp90 inhibition increases p53 expression and destabilizes MYCN and MYC in neuroblastoma

  • Authors:
    • Paul L. Regan
    • Joshua Jacobs
    • Gerald Wang
    • Jaime Torres
    • Robby Edo
    • Jennifer Friedmann
    • Xao X. Tang
  • View Affiliations

  • Published online on: January 1, 2011     https://doi.org/10.3892/ijo_00000829
  • Pages: 105-112
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Neuroblastoma is a childhood cancer that exhibits either a favorable or an unfavorable phenotype. MYCN and MYC are oncoproteins that play crucial roles in determining the malignancy of unfavorable neuroblastoma. The Hsp90 superchaperone complex assists in the folding and function of a variety of oncogenic client proteins. Inhibition of Hsp90 by small molecule inhibitors leads to the destabilization of these oncogenic proteins and consequently suppresses tumor malignancy. Nonetheless, little is known about the effect of Hsp90 inhibition on the stability of MYCN and MYC proteins. In this study, we investigated the effect of Hsp90 inhibition on the phenotype of unfavorable neuroblastoma cells including its effect on MYCN and MYC expression. Two MYCN-amplified neuroblastoma cell lines (IMR5 and CHP134) and two non-MYCN-amplified cell lines (SY5Y and SKNAS) were used to address the effect of Hsp90 inhibition on the malignant phenotype of neuroblastoma. It was found that Hsp90 inhibition in neuroblastoma cell lines resulted in significant growth suppression, a decrease in MYCN and MYC expression, and an increase in the expression of p53. In the TP53-mutated SKNAS cell line, Hsp90 inhibition enhanced the expression of the favorable neuroblastoma genes EFNB2, MIZ-1 and NTRK1 (TrkA). In addition, Hsp90 inhibition reduced HDAC6 expression and enhanced tubulin acetylation. Together our data suggest that Hsp90 inhibition suppresses the growth of neuroblastoma through multiple cellular pathways and that MYC/MYCN destabilization is among the important consequences of Hsp90 inhibition.

Related Articles

Journal Cover

January 2011
Volume 38 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Regan, P.L., Jacobs, J., Wang, G., Torres, J., Edo, R., Friedmann, J., & Tang, X.X. (2011). Hsp90 inhibition increases p53 expression and destabilizes MYCN and MYC in neuroblastoma. International Journal of Oncology, 38, 105-112. https://doi.org/10.3892/ijo_00000829
MLA
Regan, P. L., Jacobs, J., Wang, G., Torres, J., Edo, R., Friedmann, J., Tang, X. X."Hsp90 inhibition increases p53 expression and destabilizes MYCN and MYC in neuroblastoma". International Journal of Oncology 38.1 (2011): 105-112.
Chicago
Regan, P. L., Jacobs, J., Wang, G., Torres, J., Edo, R., Friedmann, J., Tang, X. X."Hsp90 inhibition increases p53 expression and destabilizes MYCN and MYC in neuroblastoma". International Journal of Oncology 38, no. 1 (2011): 105-112. https://doi.org/10.3892/ijo_00000829