The 5'-flanking region of human CD24 gene has cell-type-specific promoter activity in small-cell lung cancer.
The human surface antigen CD24 is over-expressed in small-cell lung cancer. Here we describe the isolation, sequencing and functional characterization of the 5'-flanking region of the human CD24 gene. A sequence (accession number: Y14692) of 3.4 kb regulates the activity of a luciferase reporter gene in CD24-expressing small-cell-lung-cancer cell lines up to 1.6-fold more than the control SV40 promoter and enhancer. In contrast, little or no luciferase activity was detected in 4 non-small-cell-lung-cancer cell lines. A deletion fragment of 269 bp had maximal activity in small-cell-lung-cancer cell lines (15- to 20-fold higher than control), while activity remained 2- to 10-fold below control in non-small-cell-lung-cancer cell lines. We conclude that the CD24 promoter has a strong and cell-type-specific activity, and propose its exploitation to drive the expression of therapeutic genes in small-cell lung cancer.
Pass
M K
MK
Department of Medicine, University Hospital, Zurich, Switzerland.
Quintini
G
G
Zarn
J A
JA
Zimmermann
S M
SM
Sigrist
J A
JA
Stahel
R A
RA
D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D051927:CD24 Antigen; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004273:DNA, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D051927:CD24 Antigen; C497889:CD24 protein, human; D004273:DNA, Neoplasm; D008562:Membrane Glycoproteins; D008156:Luciferases