Transcriptional repression of the human galactocerebrosidase gene in squamous cell carcinomas of the larynx

✍ Scribed by Tibor Görögh; Heinrich Rudert; Burkard M. Lippert; Stefan Gottschlich; Steffen Maune; Klaus Heidorn; Jan Maass; Markus Hoffmann; Jens E. Meyer; Immo O. Rathcke; Benedikt J. Folz; Tibor Hortobagyi; Jochen A. Werner

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: French
• Weight: 151 KB
• Volume: 83
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19991210)83:6<750::aid-ijc9>3.0.co;2-v

✦ Synopsis

Alterations of gene expression in

squamous cell carcinoma (SCC) cell lines derived from the larynx and keratinocytes derived from adjacent normal mucosa of the larynx have been studied using the mRNA differential display technique. Lane-to-lane comparison of reverse transcribed mRNA showed a strong repression of a 148 bp fragment in SCC cells. The fragment was reamplified and cloned. Sequencing revealed a 99.3% homology with a region in exon 17 of the human galactocerebrosidase (GALC) gene. Northern blot analysis confirmed the differential expression of this gene in both carcinoma cell lines and laryngeal SCC biopsies in contrast with corresponding normal mucosa. To provide further evidence for the differential expression rate, both types of cells were transiently transfected with a 152 bp (؊176 to ؊24) high regulatory promoter element of the 5Ј flanking region of the GALC gene. Results of 3 independent transfection experiments indicated a 16-fold repression of the GALC gene expression in SCC cells compared with benign keratinocytes. However, neither mutation nor other alterations of the promoter sequence were detected. Expression of the GALC gene is thus greatly affected in SCCs of the larynx.