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This version published online on December 13, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-1372
A more recent version of this article appeared on March 1, 2006
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Submitted on June 20, 2005
Accepted on December 7, 2005

The Ras Effector NORE1A is Suppressed in Follicular Thyroid Carcinomas with a PAX8-PPAR{gamma} Fusion

Theodoros Foukakis*, Amy YM Au, Göran Wallin, Janos Geli, Lars Forsberg, Roderick Clifton-Bligh, Bruce G Robinson, Weng-Onn Lui, Jan Zedenius, and Catharina Larsson

Department of Molecular Medicine and Surgery (T.F., G.W, J.G., L.F., W-O.L., J.Z., C.L), Karolinska University Hospital, SE-171 76, Stockholm, Sweden; and Cancer Genetics Unit, Kolling Institute of Medical Research (A.YM.A., R.C-B., B.G.R.), University of Sydney, Royal North Shore Hospital, New South Wales 2065, Australia

* To whom correspondence should be addressed. E-mail: Theodoros.Foukakis{at}ki.se.

Context The Ras effector NORE1A (RASSF5A) is a putative tumor suppressor and is inactivated in several human cancers. NORE1A has not been studied in thyroid cancer.

Objective To investigate whether NORE1A is involved in follicular thyroid cancer (FTC) development.

Design We analyzed NORE1A expression in 25 FTCs, 8 follicular thyroid adenomas (FTA) and 7 normal thyroid tissues by TaqMan quantitative RT-PCR. The results were evaluated in relation to RASSF1A expression, RAS mutations and PAX8-PPAR{gamma} fusions assessed in the same material. NORE1A promoter methylation was assessed by Combined Bisulfite Restriction Endonuclease Assay (CoBRA).

Results Although the NORE1A mRNA levels of the majority of the tumors were similar to the normal controls, the cases harboring a PAX8-PPAR{gamma} translocation (n = 6) exhibited dramatically reduced NORE1A expression (P < 0.001). In contrast, RAS mutations (n = 5) and NORE1A down-regulation were mutually exclusive. A significant reduction in the expression of the NORE1A homolog and bona fide tumor suppressor gene RASSF1A was observed, but with weak correlation to the respective NORE1A values. No NORE1A promoter methylation was detected in the 32 thyroid tumors analyzed.

Conclusions Our experiments demonstrate the suppression of NORE1A, a known Ras effector, in PAX8-PPAR{gamma} carrying FTCs.
Key words: Thyroid cancer • PAX8-PPAR{gamma} • NORE1 • RASSF1 • RASSF5 • RAS




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[Abstract] [Full Text] [PDF]


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