BACKGROUNDAnaplastic thyroid carcinoma (ATC) is one of the most fulminant human malignancies. However, the molecular carcinogenic mechanisms of ATC are understood poorly. Recently, the authors performed a cyclic DNA (cDNA) microarray analysis with 11 anaplastic thyroid carcinoma cell lines (ACLs) and discovered several novel responsible genes for ACLs and ATC. From the extended list, they focused on hypothetical and anonymous genes and investigated a novel gene, named the overexpressed in anaplastic thyroid carcinoma‐1 (OEATC‐1) gene.METHODSTo investigate the role of the OEATC‐1 gene in ATC carcinogenesis, first, the expression levels of OEATC‐1 in ACLs, in various types of carcinoma cell lines, and in normal human tissues were examined with reverse transcriptase‐polymerase chain reaction analysis. To explore the effect of OEATC‐1 in ATC development, a cell‐growth assay was performed with KTA2 cells under OEATC‐1 gene silencing using small‐interfering RNA (siRNA).RESULTSOEATC‐1 was overexpressed significantly in ACLs and in other types of carcinoma cell lines with various expression levels. Conversely, in normal human tissues, OEATC‐1 was expressed weakly in placenta, kidney, spleen, thymus, small intestine, and thyroid gland. To evaluate the effects of OEATC‐1 on tumor cell growth, gene silencing was caused by transfecting the plasmid‐generating siRNA effect to KTA2 cells. Consequently, the silencing of OEATC‐1 significantly suppressed the cell growth compared with controls.CONCLUSIONSThe current results indicated that OEATC‐1 may have some oncogenic or cell growth‐promoting function in ACL. OEATC‐1 is considered a novel responsible gene in ATC. Cancer 2005. © 2005 American Cancer Society.

Little is known about the genetic mechanisms of anaplastic thyroid cancer (ATC). This is the most virulent of all human malignancies, and it is believed to result from transformation of differentiated thyroid cancers. To identify a set of genes involved in the development of ATC, we investigated expression profiles of 11 cell lines derived from ATC using a cDNA microarray representing 25 344 genes. Semi-quantitative RT-PCR experiments carried out for some genes that had shown altered expression on the microarray verified frequent over-expression of destrin, HSPA8, stathmin, LDH-A, ATP5A1, PSMB6, B23, HDP-1 and LDH-B, and frequent under-expression of thyroglobulin, PBP and c-FES/FPS genes among the cell lines and also among ten primary ATCs. In addition to mRNA expression studies, up-regulation of GDI2, destrin and stathmin were confirmed with immunohistochemical analysis. The extensive list of genes identified provides valuable information towards understanding the development of ATC, and provides a source of possible biomarkers for diagnosis and/or molecular targets for the development of novel drugs to treat ATC.

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Anaplastic thyroid cancer (ATC) is one of the most fulminant and foetal diseases in human malignancies. However, the genetic alterations and carcinogenic mechanisms of ATC are still unclear. Recently, we investigated the gene expression profile of 11 anaplastic thyroid cancer cell lines (ACL) and significant decreased expression of haemoglobin beta (HBB) gene in ACL. Haemoglobin beta is located at 11p15.5, where loss of heterozygosity (LOH) was reported in various kinds of cancers, including ATC, and it has been suggested that novel tumour suppressor genes might exist in this region. In order to clarify the meaning of decreased expression of HBB in ATC, the expression status of HBB was investigated with ACL, ATC, papillary thyroid cancer (PTC) and normal human tissues. Haemoglobin beta showed significant decreased expression in ACLs and ATCs; however, in PTC, HBB expressed equal to the normal thyroid gland. In addition, HBB expressed in normal human tissues ubiquitously. To validate the tumour-suppressor function of HBB, cell growth assay was performed. Forced expression of HBB in KTA2 cell, which is a kind of ACL, significantly suppressed KTA2 growth. The mechanism of downregulation of HBB in ATC is still unclear; however, our results suggested the possibility of HBB as a novel tumour-suppressor gene.

These five genes might play an important role in deciding the behavior of node-positive breast cancer. The PI system could thus predict the prognosis of node-positive breast cancer, and might therefore be able to provide valuable information for the prognosis of breast cancer patients.