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Loss of tuberin, the tuberous‐sclerosis‐complex‐2 gene product is associated with angiogenesis
Author(s) -
NguyenVu PhuongAnh,
Fackler Ingrid,
Rust Adelheid,
DeClue Jeffrey E.,
Sander Christian A.,
Volkenandt Matthias,
Flaig Michael,
Yeung Raymond S.,
Wienecke Ralf
Publication year - 2001
Publication title -
journal of cutaneous pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 75
eISSN - 1600-0560
pISSN - 0303-6987
DOI - 10.1034/j.1600-0560.2001.028009470.x
Subject(s) - tsc2 , tuberous sclerosis , angiogenesis , biology , pathology , immunohistochemistry , cancer research , microbiology and biotechnology , medicine , pi3k/akt/mtor pathway , signal transduction
Background: Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited disorder associated with an alteration of the TSC2 tumor suppressor gene which encodes for the protein product tuberin. The disease is characterized by the development of hamartomas, e.g. cutaneous angiofibromas which consist of vascular cells, interstitial cells, and normal components of the skin. The Eker rat model, an animal model of inherited cancer, has been shown to carry a mutation of TSC2. Methods: Immunohistochemical analyses of human angiofibromas were performed using antibodies directed against tuberin and angiogenic growth factors. Proliferation of human dermal microvascular endothelial cells (HDMEC) was determined after incubation with the supernatants of TSC2 (+/+) and TSC2 (−/−) rat embryonic fibroblasts (REF) that were derived from the Eker strain. Results: Loss of the expression of tuberin was observed in the interstitial cells of 13 of 39 angiofibromas. The expression of tuberin was retained in the vascular cells. In all analyzed angiofibromas, the angiogenic factors bFGF, PD‐ECGF, VEGF and angiogenin were detected in the interstitial cells and/or vascular cells. Expression of PDGF‐B and TGF‐β1 was weak. Tissue culture supernatants from TSC2 (−/−) REF stimulated the growth of HDMEC significantly more than supernatants from TSC2 (+/+) REF. Conclusion: A functional loss of tuberin may stimulate vascular growth.