c-Myc overexpression causes anaplasia in medulloblastoma

Duncan Stearns, Aneeka Chaudhry, Ty W. Abel, Peter C. Burger, Chi V. Dang, Charles G. Eberhart

Research output: Contribution to journalArticlepeer-review

Abstract

Both anaplasia and increased c-myc gene expression have been shown to be negative prognostic indicators for survival in medulloblastoma patients. myc gene amplification has been identified in many large cell/anaplastic medulloblastoma, but no causative link between c-myc and anaplastic changes has been established. To address this, we stably overexpressed c-myc in two medulloblastoma cell lines, DAOY and UW228, and examined the changes in growth characteristics. When analyzed in vitro, cell lines with increased levels of c-myc had higher rates of growth and apoptosis as well as significantly improved ability to form colonies in soft agar compared with control. When injected s.c. into nu/nu mice, flank xenograft tumors with high levels of c-myc in DAOY cell line background were 75% larger than those derived from control. Overexpression of c-myc was required for tumor formation by UW228 cells. Most remarkably, the histopathology of the Myc tumors was severely anaplastic, with large areas of necrosis/apoptosis, increased nuclear size, and macronucleoli. Indices of proliferation and apoptosis were also significantly higher in Myc xenografts. Thus, c-myc seems to play a causal role in inducing anaplasia in medulloblastoma. Because anaplastic changes are often observed in recurrent medulloblastoma, we propose that c-myc deregulation is involved in the progression of these malignant embryonal neoplasms.

Original languageEnglish (US)
Pages (from-to)673-681
Number of pages9
JournalCancer Research
Volume66
Issue number2
DOIs
StatePublished - Jan 15 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'c-Myc overexpression causes anaplasia in medulloblastoma'. Together they form a unique fingerprint.

Cite this