AlphaB-crystallin expression in various endocrine neoplasias and identification of underlying mechanisms leading to alphaB-crystallin gene silencing in de-differentiated thyroid tumors

• Published in: Experimental and Clinical Endocrinology & Diabetes
• Main Authors: Mineva, I, Gartner, W, Hauser, P, Kainz, A, Löffler, M, Wolf, G, Oberbauer, R, Niederle, B, Weissel, M, Wagner, L
• Format: Conference Proceeding
• Language: English
• Published: 21.03.2005
• ISSN: 0947-7349; 1439-3646
• DOI: 10.1055/s-2005-863027

Introduction: The small heat shock protein family members Hsp 27 and alphaB-crystallin are thought to exert different functional properties, although both posses chaperone activity. Objective: Comparison of Hsp 27 and alphaB-crystallin expression in various endocrine neoplasias and normal endocrine tissue. Material and Methods: Immunofluorescence. Immunoblot analysis. Northern-blot analysis. Bio-informatic alphaB-crystallin and Hsp27 promoter analysis. Gene array analysis. Southern-blotting. Results: AlphaB-crystallin was found highly expressed in benign thyroid tissue but only to marginal extent in anaplastic thyroid carcinoma (ATC). In contrast, Hsp 27 was over-expressed in ATCs. Similar results were seen in other endocrine neoplasias, with varying alphaB-crystallin expression but consistently high Hsp27 expression. Bioinformatic promoter analysis revealed distinct differences within the regulatory elements of Hsp 27 and alphaB-crystallin. Comparative gene array analysis of ATC and benign thyroid tissue revealed an ATC-characteristic expression pattern of alphaB-crystallin transcription factors. Differences between ATC- and benign thyroid-derived somatic alphaB-crystallin encoding DNA were ruled out. Conclusions: In contrast to Hsp27, alphaB-crystallin is down-regulated in highly de-differentiated thyroid malignancies and exhibits varying expression in other endocrine neoplasias. The differential expression of alphaB-crystallin and Hsp27 seems to be the result of variations within the promoter regions of both proteins. As underlying cause for the down-regulation of alphaB-crystallin in ATC tissue, a tumour characteristic transcription factor expression pattern is identified.