title: Transcriptional repression of the human galactocerebrosidase gene in squamous cell carcinomas of the larynx.
abstract: 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 5' 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.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University of Kiel, Germany. gorogh@hno.uni-kiel.de
authors.forename: T
authors.initials: T
authors.lastname: Görögh
authors.forename: H
authors.initials: H
authors.lastname: Rudert
authors.forename: B M
authors.initials: BM
authors.lastname: Lippert
authors.forename: S
authors.initials: S
authors.lastname: Gottschlich
authors.forename: S
authors.initials: S
authors.lastname: Maune
authors.forename: K
authors.initials: K
authors.lastname: Heidorn
authors.forename: J
authors.initials: J
authors.lastname: Maass
authors.forename: M
authors.initials: M
authors.lastname: Hoffmann
authors.forename: J E
authors.initials: JE
authors.lastname: Meyer
authors.forename: I O
authors.initials: IO
authors.lastname: Rathcke
authors.forename: B J
authors.initials: BJ
authors.lastname: Folz
authors.forename: T
authors.initials: T
authors.lastname: Hortobagyi
authors.forename: J A
authors.initials: JA
authors.lastname: Werner
mesh_terms: D001483:Base Sequence; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D004794:Enzyme Repression; D005698:Galactosylceramidase / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D007822:Laryngeal Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D009061:Mouth Mucosa / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D005698:Galactosylceramidase