Bmx tyrosine kinase transgene induces skin hyperplasia, inflammatory angiogenesis, and accelerated wound healing.
The Bmx gene, a member of the Tec family of nonreceptor protein tyrosine kinases, is expressed in arterial endothelium and in certain hematopoietic and epithelial cells. Previous in vitro studies have implicated Bmx signaling in cell migration and survival and suggested that it contributes to the progression of prostate carcinomas. However, the function of Bmx in normal tissues in vivo is unknown. We show here that Bmx expression is induced in skin keratinocytes during wound healing. To analyze the role of Bmx in epidermal keratinocytes in vivo, we generated transgenic mice overexpressing Bmx in the skin. We show that Bmx overexpression accelerates keratinocyte proliferation and wound reepithelialization. Bmx expression also induces chronic inflammation and angiogenesis in the skin, and gene expression profiling suggests that this occurs via cytokine-mediated recruitment of inflammatory cells. Our studies provide the first data on Bmx function in vivo and form the basis of evaluation of its role in epithelial neoplasia.
Paavonen
Karri
K
Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute and Biomedicum Helsinki, University of Helsinki and Helsinki University Central Hospital, Helsinki FIN-00014, Finland.
Ekman
Niklas
N
Wirzenius
Maria
M
Rajantie
Iiro
I
Poutanen
Matti
M
Alitalo
Kari
K
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D004247:DNA / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D006965:Hyperplasia; D018836:Inflammation Mediators / Q000378:metabolism; D053547:Keratin-14; D015603:Keratinocytes / Q000201:enzymology / Q000473:pathology; D007633:Keratins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000502:physiology*; D012867:Skin / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology*; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*
D018836:Inflammation Mediators; C507540:KRT14 protein, human; D053547:Keratin-14; C507446:Krt14 protein, mouse; D007633:Keratins; D004247:DNA; C492366:Bmx protein, mouse; D011505:Protein-Tyrosine Kinases