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The Ras effector NORE1A is suppressed in follicular thyroid carcinomas with a PAX8-PPARgamma fusion

Theodoros Foukakis1, Amy Y M Au, Göran Wallin

  • 1Department of Molecular Medicine and Surgery, Karolinska University Hospital, CMM L8:01, SE-171 76 Stockholm, Sweden. theodoros.foukakis@ki.se

The Journal of Clinical Endocrinology and Metabolism
|December 15, 2005
PubMed
Abstract

Insights

NORE1A, a tumor suppressor, is suppressed in follicular thyroid cancers with PAX8-PPARgamma translocations. This Ras effector

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The Ras effector NORE1A (RASSF5A) acts as a tumor suppressor and is inactivated in various human cancers.
  • NORE1A's role in thyroid cancer has not been previously investigated.

Purpose of the Study:

  • To determine if NORE1A is implicated in the development of follicular thyroid cancer (FTC).

Main Methods:

  • Quantitative RT-PCR was used to analyze NORE1A expression in FTCs, adenomas, and normal thyroid tissues.
  • Analysis included RASSF1A expression, RAS mutations, and PAX8-PPARgamma fusions.
  • NORE1A promoter methylation was assessed using bisulfite restriction endonuclease assay.

Main Results:

  • FTCs with PAX8-PPARgamma translocations showed significantly reduced NORE1A expression.
  • RAS mutations and NORE1A down-regulation were found to be mutually exclusive.
  • A reduction in RASSF1A expression was observed, but with limited correlation to NORE1A levels.
  • No NORE1A promoter methylation was detected in any of the analyzed thyroid tumors.

Conclusions:

  • NORE1A, a Ras effector, is suppressed in FTCs that harbor PAX8-PPARgamma translocations.
  • These findings suggest a potential role for NORE1A in FTC pathogenesis, particularly in tumors with specific genetic alterations.

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