Comprehensive gene expression profiling of anaplastic thyroid cancers with cDNA microarray of 25 344 genes

Abstract

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.

Molecular profiling related to poor prognosis in thyroid carcinoma. Combining gene expression data and biological information

“…In addition, the analysis related to the dedifferentiation process confirmed over-and underexpression of genes previously described to indicate poor prognosis for thyroid tumors (Rocha et al, 2003;Onda et al, 2004;Motti et al, 2005;Pallante et al, 2005;Sorrentino et al, 2005;Zou et al, 2005; Table 4). …”

Increased expression of nucleophosmin/B23 in hepatocellular carcinoma and correlation with clinicopathological parameters

“…Nucleophosmin nuclear overexpression in colon adenoma/ carcinoma seems also to be associated with adenoma/carcinoma progression (Nozawa et al, 1996). It has been shown that NPM overexpression was present in several human solid tumours, including gastric cancer (Tanaka et al, 1992), colon cancer (Nozawa et al, 1996), bladder cancer (Tsui et al, 2004), prostate cancer (Subong et al, 1999), thyroid cancer (Onda et al, 2004), and ovary cancer (Zhang, 2004). Interestingly, a recent review reported that NPM overexpression in tumour cells led to increased proliferation and inhibition of apoptosis and was involved in human tumorigenesis (Grisendi et al, 2006).…”

“…Mounting evidence has linked excessive NPM to cellular transformation and ontogenesis (Pulford et al, 2001). Nucleophosmin overexpression is frequently found in human cancers, including cancers of the stomach (Tanaka et al, 1992), colon (Nozawa et al, 1996), bladder (Tsui et al, 2004), prostate (Subong et al, 1999), thyroid (Onda et al, 2004), ovary (Zhang, 2004), and myeloid and lymphoid cells (Schnittger et al, 2005). It has been shown that overexpression of NPM in bladder cancer is independently associated with cancer recurrence and progression to more advanced stages, suggesting that NPM overexpression is an important prognostic indicator for bladder cancer recurrence (Tsui et al, 2004).…”

Decreased expression of haemoglobin beta (HBB) gene in anaplastic thyroid cancer and recovory of its expression inhibits cell growth

“…For the comparison, five normal thyroid samples were served as a control in SQ-PCR. To adjust the amount of transcribed cDNA, GAPDH was selected as an internal control and SQ-PCR experiments were carried out as previously described, after adjustment of the amount of template cDNA (Onda et al, 2004a). The primer sequences for GAPDH were 5 0 -ggaaggtgaaggtcggagt-3 0 (forward) and 5 0 -tgggtggaatcatattggaa-3 0 (reverse).…”

“…Recently, we investigated the gene expression profile of anaplastic thyroid cancer cell lines (ACLs) with cDNA microarray analysis (Onda et al, 2004a) and found the novel gene alterations that related to ATC/ACL carcinogenesis. The results of microarray analysis showed that haemoglobin beta (HBB) gene significantly decreased expression in ACLs, compared to the expression of normal thyroid gland.…”