Role of Bone Morphogenetic Protein Signaling in Skin Carcinogenesis: Effect of Transgenic Overexpression of BMP Antagonist Noggin on Skin Tumor Development; Molecular Mechanisms Underlying Tumor Suppressive Role of BMP Signaling in Skin

    January 2009 in “ Bradford Scholars (University of Bradford) ”
    Andrei N. Mardaryev
    TLDR BMP signaling helps prevent skin tumors by blocking cancer-promoting pathways.
    The study investigated the role of bone morphogenetic protein (BMP) signaling in skin carcinogenesis using a transgenic mouse model with overexpression of the BMP antagonist Noggin. These K14-Noggin mice developed spontaneous hair follicle-derived tumors resembling human trichofolliculoma, linked to increased cell proliferation and expansion of hair follicle stem cells. The mice also exhibited hyperplasia in sebaceous glands and epidermis, leading to higher susceptibility to chemically-induced carcinogenesis. Gene expression profiling showed increased expression of pro-oncogenic pathways (Wnt, Shh, PDGF, Ras) in tumor development. Pharmacological inhibition of Wnt and Shh pathways reduced tumor initiation and progression. BMP signaling was found to suppress tumor activity by antagonizing Wnt and Shh pathways, highlighting its tumor-suppressive role in skin epithelium.
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