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P-Akt expression distinguishes two types of malignant rhabdoid tumors

Aubri Charboneau1, Jingjing Chai, Jennifer Jordan

  • 1Department of Pathology and Laboratory Medicine, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina 27599, USA.

Journal of Cellular Physiology
|August 10, 2006
PubMed

Insights

Phosphorylated Akt (P-Akt) is found in some pediatric malignant rhabdoid tumors (MRTs). P-Akt may indicate a new treatment strategy for these aggressive childhood cancers.

Area of Science:

  • Pediatric oncology
  • Molecular biology
  • Cancer genetics

Background:

  • Malignant rhabdoid tumors (MRTs) are aggressive pediatric cancers affecting the kidney and CNS.
  • Current treatments lack curative options for MRTs.
  • SNF5 tumor suppressor gene inactivation is common in MRTs, but other genetic factors are less understood.

Purpose of the Study:

  • To investigate the role of phosphorylated Akt (P-Akt) in MRT development.
  • To determine if P-Akt expression correlates with tumor characteristics or treatment sensitivity.
  • To explore potential therapeutic targets for P-Akt-positive MRTs.

Main Methods:

  • Immunohistochemical analysis of P-Akt expression in primary MRTs and MRT cell lines.
  • Assessment of P-Akt levels in relation to p21-induced growth arrest.
  • Review of existing clinical trial data for PI3-K/Akt pathway inhibitors.

Main Results:

  • P-Akt expression was detected in a subpopulation of cells in at least 10% of primary MRTs.
  • High levels of P-Akt were observed in three MRT cell lines.
  • MRTs with high P-Akt expression showed reduced sensitivity to p21-induced growth arrest.
  • P-Akt expression may differentiate MRT subtypes.

Conclusions:

  • P-Akt expression is a potential biomarker for a subset of MRTs.
  • Targeting the PI3-K/Akt pathway with specific drugs may offer a novel treatment approach for P-Akt-positive MRTs.
  • P-Akt pathway activation in MRTs suggests a link to adult malignancies.

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