Microarray analysis of UVB-regulated genes in keratinocytes: downregulation of angiogenesis inhibitor thrombospondin-1.
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.
Howell
B G
BG
Department of Dermatology, Johns Hopkins Outpatient Center, Johns Hopkins University, 601 N. Caroline Street, Room 6068, Baltimore, MD, USA.
Wang
B
B
Freed
I
I
Mamelak
A J
AJ
Watanabe
H
H
Sauder
D N
DN
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*
D019700:Thrombospondin 1