Evidence for transcriptional repression of SPARC-like 1, a gene downregulated in human lung tumors.
SPARCL1 mRNA was shown to be downregulated in NSCLC as well as in prostate, colon, and bladder carcinomas. Therefore, SPARCL1 was suggested to be a tumor suppressor gene. By microsatellite analysis, real-time quantitative PCR, and sequence analysis of all exons including the intron-exon junctions and a part of the putative promoter region, we could not find any deletion or mutation that might be responsible for the downregulation of SPARCL1 in NSCLC. We conclude that SPARCL1 is therefore not a classical tumor suppressor gene with a deletion or mutation in one allele and another mutation in the second allele. To test whether SPARCL1 could be downregulated by repression of transcription we performed luciferase reporter gene assays with 10 different SPARCL1 promoter constructs. These experiments revealed that the presence of exon 1 is able to cause a reduction in luciferase activity. Furthermore, we show that the inhibitory activity of exon 1 can be transferred to a heterologous promoter. This indicates that SPARCL1 downregulation might be mediated (at least in part) through transacting factors that bind to exon 1.
Isler
Silvia G
SG
Friedrich Miescher Institute, Novartis Research Foundation, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
Ludwig
Christian U
CU
Chiquet-Ehrismann
Ruth
R
Schenk
Susanne
S
D000368:Aged; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D008969:Molecular Sequence Data; D015676:Osteonectin / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic
D015676:Osteonectin