Overexpression of MLH-1 and psoriasin genes in cutaneous angiofibromas from tuberous sclerosis complex patients.
BACKGROUND
Tuberous sclerosis complex (TSC) is associated with mutations in two likely tumor-suppressor genes (TSC1 and TSC2) and characterized by the development of tumor-like growths (angiofibromas) in a variety of tissues and organs, particularly brain and skin.


METHODS
Employing a DNA-microarray assay, able to detect mRNA production from 1176 different basic genes, we analyzed the gene-expression levels in a cutaneous hamartoma sample from a TSC patient. Altered gene expressions detected by microarray technology were further checked by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) in the same material and in cutaneous hamartoma samples obtained from five other TSC patients.


RESULTS
The results obtained by the microarray technology in one hamartoma specimen, confirmed by the RT-PCR results obtained in the same material and in five other hamartoma specimens, demonstrated that TSC-related angiofibromas exhibit significant mRNA overexpression of two genes, represented by MLH-1 and psoriasin.


CONCLUSIONS
The overexpression of MLH-1, which codes for a DNA mismatch repair protein, and psoriasin, which codes for a specific chemoattractant factor for CD4+ T cells, implicated in the pathogenesis of inflammatory skin disease, and expressed in excess during abnormal pathways of cell growth, may shed light on the pathogenesis of the proliferative skin lesion.
La Placa
Michelangelo
M
Department of Clinical and Experimental Medicine, Dermatology Section, University of Bologna, Bologna, Italy. dermolap@med.unibo.it
Gibellini
Davide
D
Bianchi
Tommaso
T
Patrizi
Annalisa
A
D048868:Adaptor Proteins, Signal Transducing; D018322:Angiofibroma / Q000209:etiology / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics*; D014402:Tuberous Sclerosis / Q000150:complications / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; D000070957:MutL Protein Homolog 1