title: Microarray analysis of UVB-regulated genes in keratinocytes: downregulation of angiogenesis inhibitor thrombospondin-1.
abstract: BACKGROUND
  Ultraviolet (UV) B light is an environmental mutagen that induces changes in cutaneous gene expression leading to immune suppression and carcinogenesis. Keratinocytes are a primary target for UVB.
  
  
  OBJECTIVE
  To further delineate UVB-induced gene expression changes in keratinocytes.
  
  
  METHODS
  cDNA microarray technology was utilized to examine gene expression in normal human KC (NHKC) following 20 mJcm(-2) UVB irradiation. Data was confirmed by semi-quantitative RT-PCR.
  
  
  RESULTS
  Microarray analysis revealed 57 genes were upregulated, and 27 genes were downregulated, by at least two-fold following UVB. One downregulated gene was the endogenous angiogenesis inhibitor thrombospondin-1 (TSP-1). Semi-quantitative RT-PCR confirmed persistent downregulation of TSP-1 up to 18h following UVB. Microarray analysis also revealed upregulation of platelet-derived endothelial cell growth factor (PD-ECGF)--an angiogenesis activator.
  
  
  CONCLUSIONS
  Our results suggest a gene expression mechanism by which UVB induces an angiogenic switch in keratinocytes. This may represent an important early event promoting neovascularization and growth of cutaneous neoplasms.
authors.affiliation: Department of Dermatology, Johns Hopkins Outpatient Center, Johns Hopkins University, 601 N. Caroline Street, Room 6068, Baltimore, MD, USA.
authors.forename: B G
authors.initials: BG
authors.lastname: Howell
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.forename: I
authors.initials: I
authors.lastname: Freed
authors.forename: A J
authors.initials: AJ
authors.lastname: Mamelak
authors.forename: H
authors.initials: H
authors.lastname: Watanabe
authors.forename: D N
authors.initials: DN
authors.lastname: Sauder
mesh_terms: D002478:Cells, Cultured; D015536:Down-Regulation / Q000528:radiation effects; D015870:Gene Expression / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis; D012878:Skin Neoplasms / Q000209:etiology / Q000503:physiopathology; D019700:Thrombospondin 1 / Q000235:genetics*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D019700:Thrombospondin 1