Overexpression of hepatocyte growth factor/scatter factor promotes vascularization and granulation tissue formation in vivo

Toyoda, Mitsuo; Takayama, Hisashi; Horiguchi, Norio; Otsuka, Toshiyuki; Fukusato, Toshio; Merlino, Glenn; Takagi, Hitoshi; Mori, Masatomo

doi:10.1016/s0014-5793(01)03126-x

Cited by 75 publications

(50 citation statements)

References 41 publications

(52 reference statements)

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“…15 Hepatocyte growth factor has a significant effect on vascularization and granulation tissue formation during wound healing in vivo. 31 Moreover, HGF stimulates wound healing, with less susceptibility to cutaneous scarring. 32 In this study, re-epithelialization and microvasculation of the wound were promoted after HGF gene transfer.…”

Section: Discussionmentioning

confidence: 99%

Acceleration of wound healing by combined gene transfer of hepatocyte growth factor and prostacyclin synthase with Shima Jet

et al. 2006

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Section: Discussionmentioning

confidence: 99%

Acceleration of wound healing by combined gene transfer of hepatocyte growth factor and prostacyclin synthase with Shima Jet

et al. 2006

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“…This region contains the classical AP-2 consensus element 5Ј-GCC-NNNGGC-3Ј (30), which has been shown to mediate induction of VEGF expression induced by serum withdrawal, UVA exposure (31), transforming growth factor (TGF) -␣ (27), hepatocyte growth factor (32,33), and epidermal growth factor (34) stimulation. Although these studies show that Sp1 binds to this region to stimulate VEGF expression, mutations in the AP-2 consensus element from GCCGGGGGC to GCCTAGGGC reduced TGF-␣ and UVA-mediated induction by 50%.…”

Section: Discussionmentioning

confidence: 99%

Activator Protein 2α Inhibits Tumorigenicity and Represses Vascular Endothelial Growth Factor Transcription in Prostate Cancer Cells

et al. 2004

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Activator protein-2␣ (AP-2) is a transcription factor that regulates proliferation and differentiation in mammalian cells. We have shown previously that although AP-2 is expressed highly in normal prostatic epithelium, its expression is lost in high-grade prostatic intraepithelial neoplasia and prostate cancer, suggesting that loss of AP-2 plays a role in prostate cancer development. We demonstrate that forced AP-2 expression in the prostate cancer cell line LNCaP-LN3 (AP-2 negative) inhibited dramatically tumor incidence in nude mice. To identify the genes that might have been responsible for this effect, we used microchip expression array. We found several genes known to be involved in malignancy were deregulated, including the vascular endothelial growth factor (VEGF) gene. Because VEGF was down-regulated by 14.7-fold in the AP-2-transfected cells and because it is a major angiogenic factor in prostate cancer development and progression, we chose to examine the AP-2-VEGF interaction. Our evidence suggests that AP-2 repressed transcriptionally the VEGF promoter by competing with the transcriptional activator Sp3. Loss of AP-2 in prostate cancer cells reduced the AP-2:Sp3 ratio and activated VEGF expression. AP-2 acts as a tumor-suppressor gene in prostate cancer. Elucidating the molecular events resulting from loss of AP-2 in the prostate epithelium has implications for the understanding and prevention of the onset of prostate cancer.

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“…Moreover, the activation of the Met receptor promotes angiogenesis and wound healing in mice (Toyoda et al, 2001;Horiguchi et al, 2002), and evidence indicates a role in primitive hematopoiesis during early Xenopus development (Koibuchi et al, 2004). In cell culture systems, the HGF/Met receptor has been shown to affect many cellular functions, including mitogenesis of hepatocytes and myoblasts, cell scattering, invasion and branching tubulogenesis of epithelial cells as well as chemoattraction of motor neurons (for reviews, see Birchmeier et al, 2003;Zhang and Vande Woude, 2003).…”

Section: Introductionmentioning

confidence: 99%

Gab1 Is Required for Cell Cycle Transition, Cell Proliferation, and Transformation Induced by an Oncogenic Met Receptor

Mood

Saucier

Bong

et al. 2006

MBoC

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We have shown previously that either Grb2-or Shc-mediated signaling from the oncogenic Met receptor Tpr-Met is sufficient to trigger cell cycle progression in Xenopus oocytes. However, direct binding of these adaptors to Tpr-Met is dispensable, implying that another Met binding partner mediates these responses. In this study, we show that overexpression of Grb2-associated binder 1 (Gab1) promotes cell cycle progression when Tpr-Met is expressed at suboptimal levels. This response requires that Gab1 possess an intact Met-binding motif, the pleckstrin homology domain, and the binding sites for phosphatidylinositol 3-kinase and tyrosine phosphatase SHP-2, but not the Grb2 and CrkII/phospholipase C␥ binding sites. Importantly, we establish that Gab1-mediated signals are critical for cell cycle transition promoted by the oncogenic Met and fibroblast growth factor receptors, but not by progesterone, the natural inducer of cell cycle transition in Xenopus oocytes. Moreover, Gab1 is essential for Tpr-Met-mediated morphological transformation and proliferation of fibroblasts. This study provides the first evidence that Gab1 is a key binding partner of the Met receptor for induction of cell cycle progression, proliferation, and oncogenic morphological transformation. This study identifies Gab1 and its associated signaling partners as potential therapeutic targets to impair proliferation or transformation of cancer cells in human malignancies harboring a deregulated Met receptor.

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Overexpression of hepatocyte growth factor/scatter factor promotes vascularization and granulation tissue formation in vivo

Cited by 75 publications

References 41 publications

Acceleration of wound healing by combined gene transfer of hepatocyte growth factor and prostacyclin synthase with Shima Jet

Acceleration of wound healing by combined gene transfer of hepatocyte growth factor and prostacyclin synthase with Shima Jet

Activator Protein 2α Inhibits Tumorigenicity and Represses Vascular Endothelial Growth Factor Transcription in Prostate Cancer Cells

Gab1 Is Required for Cell Cycle Transition, Cell Proliferation, and Transformation Induced by an Oncogenic Met Receptor

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