TY - JOUR
T1 - The Ras effector NORE1A is suppressed in follicular thyroid carcinomas with a PAX8-PPARγ fusion
AU - Foukakis, Theodoros
AU - Au, Amy Y.M.
AU - Wallin, Göran
AU - Geli, Janos
AU - Forsberg, Lars
AU - Clifton-Bligh, Roderick
AU - Robinson, Bruce G.
AU - Lui, Weng Onn
AU - Zedenius, Jan
AU - Larsson, Catharina
PY - 2006/3
Y1 - 2006/3
N2 - 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: The objective of this study was to investigate whether NORE1A is involved in follicular thyroid cancer (FTC) development. Design: We analyzed NORE1A expression in 25 FTCs, eight follicular thyroid adenomas, and seven normal thyroid tissues by TaqMan quantitative RT-PCR. The results were evaluated in relation to RASSF1A expression, RAS mutations, and PAX8-PPARγ fusions assessed in the same material. NORE1A promoter methylation was assessed by the combined bisulfite restriction endonuclease assay. Results: Although the NORE1A mRNA levels of the majority of the tumors were similar to those in the normal controls, the cases harboring a PAX8-PPARγ 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 the 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-PPARγ carrying FTCs.
AB - 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: The objective of this study was to investigate whether NORE1A is involved in follicular thyroid cancer (FTC) development. Design: We analyzed NORE1A expression in 25 FTCs, eight follicular thyroid adenomas, and seven normal thyroid tissues by TaqMan quantitative RT-PCR. The results were evaluated in relation to RASSF1A expression, RAS mutations, and PAX8-PPARγ fusions assessed in the same material. NORE1A promoter methylation was assessed by the combined bisulfite restriction endonuclease assay. Results: Although the NORE1A mRNA levels of the majority of the tumors were similar to those in the normal controls, the cases harboring a PAX8-PPARγ 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 the 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-PPARγ carrying FTCs.
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U2 - 10.1210/jc.2005-1372
DO - 10.1210/jc.2005-1372
M3 - Article
C2 - 16352687
AN - SCOPUS:33644826974
SN - 0021-972X
VL - 91
SP - 1143
EP - 1149
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 3
ER -