Hepatoma‐derived growth factor (<i>HDGF</i>) is dispensable for normal mouse development

Gallitzendoerfer, Rainer; Abouzied, Mekky M.; Hartmann, Dieter; Dobrowolski, Radoslaw; Gieselmann, Volkmar; Franken, Sebastian

doi:10.1002/dvdy.21589

Cited by 21 publications

(25 citation statements)

References 54 publications

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“…Our apparent finding that HDGF does not affect apoptosis is surprising, given that HDGF overexpression inhibits caspase 3 activity in cancer cells (Liao et al 2010). However, consistent with our observations, in healthy mouse fibroblasts, HDGF is dispensable for apoptotic signaling (Gallitzendoerfer et al 2008). Alternatively, this unexpected result may be an artifact reflecting the fact that a certain percentage of cells showing unequivocal morphological signs of apoptosis fail to show TUNEL staining (Leidenfrost et al 2011).…”

Section: Day 7 Blastocysts (%)supporting

confidence: 72%

Hepatoma-derived growth factor: from the bovine uterus to the in vitro embryo culture

Gómez¹,

Correia-Álvarez²,

Caamaño³

et al. 2014

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Early in cow embryo development, hepatoma-derived growth factor (HDGF) is detectable in uterine fluid. The origin of HDGF in maternal tissues is unknown, as is the effect of the induction on developing embryos. Herein, we analyze HDGF expression in day 8 endometrium exposed to embryos, as well as the effects of recombinant HDGF (rHDGF) on embryo growth. Exposure to embryos did not alter endometrial levels of HDGF mRNA or protein. HDGF protein localized to cell nuclei in the luminal epithelium and superficial glands and to the apical cytoplasm in deep glands. After uterine passage, levels of embryonic HDGF mRNA decreased and HDGF protein was detected only in the trophectoderm. In fetal fibroblast cultures, addition of rHDGF promoted cell proliferation. In experiments with group cultures of morulae in protein-free medium containing polyvinyl alcohol, adding rHDGF inhibited blastocyst development and did not affect cell counts when the morulae were early (day 5), whereas it enhanced blastocyst development and increased cell counts when the morulae were compact (day 6). In cultures of individual day 6 morulae, adding rHDGF promoted blastocyst development and increased cell counts. Our experiments with rHDGF indicate that the growth factor stimulates embryonic development and cell proliferation. HDGF is synthesized similarly by the endometrium and embryo, and it may exert embryotropic effects by autocrine and/or paracrine mechanisms.

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Section: Day 7 Blastocysts (%)supporting

confidence: 72%

Hepatoma-derived growth factor: from the bovine uterus to the in vitro embryo culture

Gómez¹,

Correia-Álvarez²,

Caamaño³

et al. 2014

Reproduction

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“…Furthermore HDGF has been suggested to be neurotrophic and involved in organ development and regeneration [5,7,9,11-15]. However, no obvious biochemical or morphological phenotype could be detected in a HDGF-deficient mouse model [16]. …”

Section: Introductionmentioning

confidence: 99%

Hepatoma-derived growth factor and nucleolin exist in the same ribonucleoprotein complex

et al. 2013

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BackgroundHepatoma-derived growth factor (HDGF) is a protein which is highly expressed in a variety of tumours. HDGF has mitogenic, angiogenic, neurotrophic and antiapoptotic activity but the molecular mechanisms by which it exerts these activities are largely unknown nor has its biological function in tumours been elucidated. Mass spectrometry was performed to analyse the HDGFStrep-tag interactome. By Pull–down-experiments using different protein and nucleic acid constructs the interaction of HDGF and nucleolin was investigated further.ResultsA number of HDGFStrep-tag copurifying proteins were identified which interact with RNA or are involved in the cellular DNA repair machinery. The most abundant protein, however, copurifying with HDGF in this approach was nucleolin. Therefore we focus on the characterization of the interaction of HDGF and nucleolin in this study. We show that expression of a cytosolic variant of HDGF causes a redistribution of nucleolin into the cytoplasm. Furthermore, formation of HDGF/nucleolin complexes depends on bcl-2 mRNA. Overexpression of full length bcl-2 mRNA increases the number of HDGF/nucleolin complexes whereas expression of only the bcl-2 coding sequence abolishes interaction completely. Further examination reveals that the coding sequence of bcl-2 mRNA together with either the 5′ or 3′ UTR is sufficient for formation of HDGF/nucleolin complexes. When bcl-2 coding sequence within the full length cDNA is replaced by a sequence coding for secretory alkaline phosphatase complex formation is not enhanced.ConclusionThe results provide evidence for the existence of HDGF and nucleolin containing nucleoprotein complexes which formation depends on the presence of specific mRNAs. The nature of these RNAs and other components of the complexes should be investigated in future.

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“…In case of HSF1-deprivation tumor cells die and tumors regress whereas normal cells do not depend on this protein [51]. The latter certainly applies for HDGF as shown by the normal development and health of HDGF -/- mice [15]. On the other hand, in vitro and in vivo experiments showed that a reduction of HDGF in transformed cells or the injection of HDGF specific antibodies resulted in slowed tumor growth, reduced number of blood vessels, and increased rate of apoptosis [25,52-54].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the following mouse lines were generated by backcrossing: HDGF Tyr /HDGF -/- , HDGF Tyr /Ink4a -/- , HDGF -/- /Ink4a -/- . The HDGF -/- mouse line was generated by Rainer Gallitzendörfer (IBMB, University of Bonn, Germany) [15], whereas the Ink4a -/- mice were kindly provided by Clemens Schmitt (Charité - University Berlin, Germany) with permission of Manuel Serrano (Spanish National Cancer Research Centre, Madrid, Spain) [29]. …”

Section: Methodsmentioning

confidence: 99%

“…This suggestion was supported by the classification of HDGF as an alarmin, a protein signaling cell and tissue damage to the immune system [13,14]. Surprisingly, HDGF-knockout (HDGF -/- ) mice are viable and show no developmental phenotype [15]. Over the last years, the overexpression of HDGF in various tumors attracted more and more attention.…”

Section: Introductionmentioning

confidence: 99%

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Overexpression of hepatoma-derived growth factor in melanocytes does not lead to oncogenic transformation

et al. 2011

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BackgroundHDGF is a growth factor which is overexpressed in a wide range of tumors. Importantly, expression levels were identified as a prognostic marker in some types of cancer such as melanoma.MethodsTo investigate the presumed oncogenic/transforming capacity of HDGF, we generated transgenic mice overexpressing HDGF in melanocytes. These mice were bred with mice heterozygous for a defective copy of the Ink4a tumor suppressor gene and were exposed to UV light to increase the risk for tumor development both genetically and physiochemically. Mice were analyzed by immunohistochemistry and Western blotting. Furthermore, primary melanocytes were isolated from different strains created.ResultsTransgenic animals overexpressed HDGF in hair follicle melanocytes. Interestingly, primary melanocytes isolated from transgenic animals were not able to differentiate in vitro whereas cells isolated from wild type and HDGF-deficient animals were. Although, HDGF-/-/Ink4a+/- mice displayed an increased number of epidermoid cysts after exposure to UV light, no melanomas or premelanocytic alterations could be detected in this mouse model.ConclusionsThe results therefore provide no evidence that HDGF has a transforming capacity in tumor development. Our results in combination with previous findings point to a possible role in cell differentiation and suggest that HDGF promotes tumor progression after secondary upregulation and may represent another protein fitting into the concept of non-oncogene addiction of tumor tissue.

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Hepatoma‐derived growth factor (HDGF) is dispensable for normal mouse development

Cited by 21 publications

References 54 publications

Hepatoma-derived growth factor: from the bovine uterus to the in vitro embryo culture

Hepatoma-derived growth factor: from the bovine uterus to the in vitro embryo culture

Hepatoma-derived growth factor and nucleolin exist in the same ribonucleoprotein complex

Overexpression of hepatoma-derived growth factor in melanocytes does not lead to oncogenic transformation

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