Keratinocyte growth factor: effects on keratinocytes and mechanisms of action

Keller, Ulrich auf dem; Krampert, Monika; Kümin, Angelika; Braun, Susanne; Werner, Sabine

doi:10.1078/0171-9335-00389

Cited by 68 publications

(45 citation statements)

References 39 publications

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“…Fgf7, Fgf10, and Fgf22 transduce signals through Fgfr2b in skin epidermis (18). Mice with conditional Fgfr2b knockout in skin epidermis show increased occurrence of squamous cell carcinoma (SCC) with oncogenic Hras mutations after DMBA/TPA treatment, indicating that loss of Fgfr2b in skin epidermis results in increased sensitivity to chemical carcinogenesis (44).…”

Section: Anti-oncogenic Fgfr2bmentioning

confidence: 99%

“…FGF7, FGF10 and FGF22 transduce signals through FGFR2b on epithelial cells to regulate embryogenesis and adult tissue homeostasis (18). FGF signaling cascades interact with WNT, Notch, Hedgehog and BMP signaling cascades to constitute the stem cell signaling network (22,23).…”

Section: Fgfr2-related Pathogenesis and Fgfr2-targeted Therapeutics (mentioning

confidence: 99%

“…FGF7, induced by PDGF, IL-1, IL-1ß or TNF-·, is secreted from fibroblast, smooth muscle cells, endothelial cells, skin dermis, and Á‰T cells to promote tissue repair (16)(17)(18). FGF10 is secreted from mesenchymal cells to orchestrate morphogenesis of gastrointestinal tract, respiratory tract, limb, and other organs or tissues (19,20).…”

Section: Introductionmentioning

confidence: 99%

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FGFR2-related pathogenesis and FGFR2-targeted therapeutics (Review)

Katoh¹

2009

Int J Mol Med

117

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Abstract. FGFR2 gene at human chromosome 10q26 encodes FGFR2b and FGFR2c isoforms functioning as FGF receptors with distinct expression domain and ligand specificity. FGFR2 plays oncogenic and anti-oncogenic roles in a contextdependent manner. Single nucleotide polymorphisms (SNPs) within intron 2 of FGFR2 gene are associated with breast cancer through allelic FGFR2 upregulation. Missense mutations or copy number gains of FGFR2 gene occur in breast cancer and gastric cancer to activate FGFR2 signaling. Aberrant FGFR2 signaling activation induces proliferation and survival of tumor cells. The class switch from FGFR2b to FGFR2c occurs during progression of prostate cancer and bladder cancer because of spliceosome dysregulation. In addition, epidermal Fgfr2b knockout mice show increased sensitivity to chemical carcinogenesis partly due to the failure of Nfe2l2 (Nrf2)-mediated detoxification of reactive oxygen species (ROS). Loss of FGFR2b signaling induces epithelialto-mesenchymal transition (EMT) and unruly ROS. FGFR2 signaling dysregulation due to the accumulation of epigenetic modifications and genetic alterations during chronic inflammation, smoking, increased caloric uptake, and decreased exercise leads to carcinogenesis. PD173074, SU5402, AZD2171, and Ki23057 are small-molecule FGFR inhibitors. Human antibody, peptide mimetic, RNA aptamer, siRNA, and synthetic microRNA (miRNA) are emerging technologies to be applied for cancer therapeutics targeted to FGFR2. Because novel sequence technology and peta-scale supercomputer are opening up the sequence era following the genome era, personalized medicine prescribing targeted drugs based on germline and/or somatic genomic information is coming reality. Application of FGFR2 inhibitors for cancer treatment in patients with FGFR2 mutation or gene amplification is beneficial; however, that for cancer prevention in people with FGFR2 risk allele might be disadvantageous due to the impediment of a cytoprotective mechanism against oxidative stress.

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Section: Anti-oncogenic Fgfr2bmentioning

confidence: 99%

Section: Fgfr2-related Pathogenesis and Fgfr2-targeted Therapeutics (mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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FGFR2-related pathogenesis and FGFR2-targeted therapeutics (Review)

Katoh¹

2009

Int J Mol Med

117

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“…Transdifferentiated ESCs obtained from the skin (Watt et al, 2006) can both self-renew and produce differentiated progeny, which is beneficial in the formation of hair follicles and sweat glands (Qiao et al, 2008). Furthermore, KGF is known to regulate the migration, proliferation, differentiation, and survival of keratinocytes (Auf dem Keller et al, 2004). Several studies also suggested that KGF can increase the resistance of epithelial cells by altering the expression of mediators or antagonists of apoptosis (Buckley et al, 1998) or by altering the ability of cells to scavenge free radicals (Beeret et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Keratinocyte growth factor (KGF), a monomeric peptide that belongs to the fibroblast growth factor (FGF) family (Branski et al, 2007), is produced by cells of mesenchymal origin and mediates epithelial cell proliferation and differentiation in a variety of tissues such as lung and skin (Auf dem Keller et al, 2004;Yu et al, 2010). This paracrine action of KGF on epithelial cells is mediated through the KGF receptor, a splice variant of the FGF-2 receptor encoded by the FGF receptor gene.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Adenoviral Transfection of the Keratinocyte Growth Factor Gene on Epidermal Stem Cells: an In Vitro Study

Liang

Zhao

et al. 2013

Molecules and Cells

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Epidermal stem cells (ESCs) are characterized as slowcycling, multi-potent, and self-renewing cells that not only maintain somatic homeostasis but also participate in tissue regeneration and repair. To examine the feasibility of adenoviral vector-mediated keratinocyte growth factor (KGF) gene transfer into in vitro-expanded ESCs, ESCs were isolated from samples of human skin, cultured in vitro, and then transfected with recombinant adenovirus (Ad) carrying the human KGF gene (AdKGF) or green fluorescent protein gene (AdGFP). The effects of KGF gene transfer on cell proliferation, cell cycle arrest, cell surface antigen phenotype, and β-catenin expression were investigated. Compared to ESCs transfected with AdGFP, AdKGFtransfected ESCs grew well, maintained a high proliferative capacity in keratinocyte serum-free medium, and expressed high levels of β-catenin. AdKGF infection increased the number of ESCs in the G0/G1 phase and promoted ESCs entry into the G2/M phase, but had no effect on cell surface antigen phenotype (CD49f + /CD71 -). The results suggest that KGF gene transfer can stimulate ESCs to grow and undergo cell division, which can be applied to enhance cutaneous wound healing.

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Molecular signatures classify astrocytic gliomas by IDH1 mutation status

Toedt

Barbus

Wolter

et al. 2010

Intl Journal of Cancer

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To identify novel glioma‐associated pathomechanisms and molecular markers, we performed an array‐based comparative genomic hybridization analysis of 131 diffuse astrocytic gliomas, including 87 primary glioblastomas (pGBIV), 13 secondary glioblastomas (sGBIV), 19 anaplastic astrocytomas (AAIII) and 12 diffuse astrocytomas (AII). All tumors were additionally screened for IDH1 and IDH2 mutations. Expression profiling was performed for 74 tumors (42 pGBIV, 11 sGBIV, 13 AAIII, 8 AII). Unsupervised and supervised bioinformatic analyses revealed distinct genomic and expression profiles separating pGBIV from the other entities. Classifier expression signatures were strongly associated with the IDH1 gene mutation status. Within pGBIV, the rare subtype of IDH1 mutant tumors shared expression profiles with IDH1 mutant sGBIV and was associated with longer overall survival compared with IDH1 wild‐type tumors. In patients with IDH1 wild‐type pGBIV, PDGFRA gain or amplification as well as 19q gain were associated with patient outcome. Array‐CGH analysis additionally revealed homozygous deletions of the FGFR2 gene at 10q26.13 in 2 pGBIV, with reduced FGFR2 mRNA levels being frequent in pGBIV and linked to poor outcome. In conclusion, we report that diffuse astrocytic gliomas can be separated into 2 major molecular groups with distinct genomic and mRNA profiles as well as IDH1 gene mutation status. In addition, our results suggest FGFR2 as a novel glioma‐associated candidate tumor suppressor gene on the long arm of chromosome 10.

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Keratinocyte growth factor: effects on keratinocytes and mechanisms of action

Cited by 68 publications

References 39 publications

FGFR2-related pathogenesis and FGFR2-targeted therapeutics (Review)

FGFR2-related pathogenesis and FGFR2-targeted therapeutics (Review)

The Effects of Adenoviral Transfection of the Keratinocyte Growth Factor Gene on Epidermal Stem Cells: an In Vitro Study

Molecular signatures classify astrocytic gliomas by IDH1 mutation status

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