Fibrous papule of the face, similar to tuberous sclerosis complex-associated angiofibroma, shows activation of the mammalian target of rapamycin pathway: evidence for a novel therapeutic strategy?

Fibrous papules of the face are hamartomas characterized by stellate-shaped stromal cells, multinucleated giant cells, and proliferative blood vessels in the dermis. The pathogenesis of fibrous papules remains unclear. There is a striking microscopic resemblance between fibrous papules and tuberous...

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Bibliographic Details
Published in:PloS one 2014-02, Vol.9 (2), p.e89467-e89467
Main Authors: Chan, Jung-Yi Lisa, Wang, Kuo-Hsien, Fang, Chia-Lang, Chen, Wei-Yu
Format: Article
Language:English
Subjects:
Activation
Analysis
Angiofibroma - pathology
Biology
Blood vessels
Dermatology
Dermis
Enzyme Activation
Face - pathology
Fibroblasts
Giant cells
Hamartoma - drug therapy
Hamartoma - pathology
Health aspects
Hospitals
Humans
Immunoglobulins
Immunohistochemistry
Keratinocytes
Kidneys
Kinases
Mammals
Medicine
Mutation
Pathogenesis
Pathology
Phosphorylation
Rapamycin
Review boards
Ribosomal protein S6
Ribosomal protein S6 kinase
Ribosomal Protein S6 Kinases, 70-kDa - metabolism
Skin
Stromal cells
TOR protein
TOR Serine-Threonine Kinases - metabolism
Tuberous sclerosis
Tuberous Sclerosis - pathology
Tuberous Sclerosis Complex 1
Tuberous Sclerosis Complex 2
Tumor Suppressor Proteins - genetics
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Summary:Fibrous papules of the face are hamartomas characterized by stellate-shaped stromal cells, multinucleated giant cells, and proliferative blood vessels in the dermis. The pathogenesis of fibrous papules remains unclear. There is a striking microscopic resemblance between fibrous papules and tuberous sclerosis complex (TSC)-associated angiofibromas. A germline mutation of the TSC1 or TSC2 gene, leading to activation of the mammalian target of rapamycin (mTOR) pathway, accounts for the pathogenesis of TSC-associated angiofibromas. Activated mTOR subsequently activates p70 ribosomal protein S6 kinase (p70S6K) and ribosomal protein S6 (S6) by phosphorylation. Rapamycin, a mTOR inhibitor, is effective in treating TSC-associated angiofibromas. The aim of this study was to understand whether the mTOR pathway is activated in fibrous papules. We studied immunoexpressions of phosphorylated (p-) mTOR effectors in fibrous papules, TSC-associated angiofibromas, and normal skin controls. P-mTOR, p-p70S6K and p-S6 were highly expressed in dermal stromal cells and epidermal keratinocytes in fibrous papules and TSC-associated angiofibromas but not in fibroblasts and epidermal keratinocytes of normal skin controls (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0089467