Transgenic overexpression of the proprotein convertase furin enhances skin tumor growth.

Neoplasia : an International Journal for Oncology Research
Jian FuAndres J P Klein-Szanto

Abstract

Furin, one of the members of the family of proprotein convertases (PCs), ubiquitously expressed as a type I membrane-bound proteinase, activates several proteins that contribute to tumor progression. In vitro studies using cancer cell lines and clinical specimens demonstrated that furin processes important substrates such as insulin-like growth factor 1 receptor (IGF-1R) and transforming growth factor β, leading to increased tumor growth and progression. Despite the numerous studies associating furin with tumor development, its effects in preclinical models has not been comprehensively studied. In this study, we sought to determine the protumorigenic role of furin in vivo after a two-stage chemical carcinogenesis protocol in transgenic mice in which furin expression was targeted to the epidermal basal layer. We found that processing of the PC substrate IGF-1R and the proliferation rate of mouse epidermis was enhanced in transgenic mice when compared with their WT counterparts. Histopathologic diagnoses of the tumors demonstrated that furin transgenic mice (line F47) developed twice as many squamous carcinomas as the control, WT mice (P < .002). Similarly, tumors cells from transgenic mice were able to process PC substrates more...Continue Reading

Citations

Jul 15, 2015·BioMed Research International·Jeroen DeclercqJohn W M Creemers
Apr 4, 2017·International Journal of Cancer. Journal International Du Cancer·Patricia Jaaks, Michele Bernasconi
Jul 3, 2015·BioMed Research International·Jeroen DeclercqJohn W Creemers
Dec 8, 2015·Molecular Therapy Oncolytics·Olga V MatveevaPeter M Chumakov

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