RETRACTED: Hepatocyte Growth Factor-Induced Expression of Ornithine Decarboxylase, c-met,and c-mycIs Differently Affected by Protein Kinase Inhibitors in Human Hepatoma Cells HepG2

Desiderio, Maria Alfonsina; Pogliaghi, Giovanna; Dansi, Paola

doi:10.1006/excr.1998.4073

Cited by 29 publications

(21 citation statements)

References 40 publications

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“…The HGF regulation of c-fos via the PI3K/Akt pathway has been studied previously (32). HGF has also been shown to regulate the activity of ornithine decarboxylase and its downstream product, intracellular polyamines, through PI3K, protein kinase C, and pp60 c-src (8). HGF regulation of Egr-1 has been shown to occur via protein kinase C and ERK MAPK, but the role of Akt is unknown (37).…”

Section: Discussionmentioning

confidence: 97%

Hepatocyte growth factor regulates cyclooxygenase-2 expression via β-catenin, Akt, and p42/p44 MAPK in human bronchial epithelial cells

Lee¹,

Suzuki²,

Griffin³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Hepatocyte growth factor (HGF) is upregulated in response to lung injury and has been implicated in tissue repair through its antiapoptotic and proliferative activities. Cyclooxygenase-2 (COX-2) is an inducible enzyme in the biosynthetic pathway of prostaglandins, and its activation has been shown to play a role in cell growth. Here, we report that HGF induces gene transcription of COX-2 in human bronchial epithelial cells (HBEpC). Treatment of HBEpC with HGF resulted in phosphorylation of the HGF receptor (c-Met), activation of Akt, and upregulation of COX-2 mRNA. Adenovirus-mediated gene transfer of a dominant negative (DN) Akt mutant revealed that HGF increased COX-2 mRNA in an Akt-dependent manner. COX-2 promoter analysis in luciferase reporter constructs showed that HGF regulation required the beta-catenin-responsive T cell factor-4 binding element (TBE). The HGF activation of the COX-2 gene transcription was blocked by DN mutant of beta-catenin or by inhibitors that blocked activation of Akt. Inhibition of p42/p44 MAPK pathway blocked HGF-mediated activation of beta-catenin gene transcription but not Akt activation, suggesting that p42/p44 MAPK acts in a parallel mechanism for beta-catenin activation. We also found that inhibition of COX-2 with NS-398 blocked HGF-induced growth in HBEpC. Together, the results show that the HGF increases COX-2 gene expression via an Akt-, MAPK-, and beta-catenin-dependent pathway in HBEpC.

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Section: Discussionmentioning

confidence: 97%

Hepatocyte growth factor regulates cyclooxygenase-2 expression via β-catenin, Akt, and p42/p44 MAPK in human bronchial epithelial cells

Lee¹,

Suzuki²,

Griffin³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…51 In human hepatoma HepG2 cells, hepatocyte growth factor (HGF) induces ODC activity in 4 h. However, expression of ODC mRNA occurs in 8-10 h. 35 The induction of ODC activity by HGF is blocked by different protein kinase inhibitors, including a PKC inhibitor, H7. 35 ODC activity induced by HGF seemed to be regulated posttranscriptionally and PKC might be involved in this regulatory process. In the studies of PKCδ transgenic mice, there is a significantly greater increase in TPA-induced epidermal ODC activity than their wild-type littermates.…”

Section: Discussionmentioning

confidence: 99%

“…(B) Levels of Bcl-2 relative to α-tubulin were determined by densitometry analysis of the immunoblotting and statistical results were calculated for at least three independent experiments. * p < 0.05. later than its activity, [33][34][35] indicating that posttranslational regulation play a role in the induction of ODC activity. There are multiple forms of ODC found in various tissues and cells by isoelectric focusing analyses.…”

Section: Discussionmentioning

confidence: 99%

Increasing ornithine decarboxylase activity is another way of prolactin preventing methotrexate-induced apoptosis: Crosstalk between ODC and BCL-2

et al. 2006

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Prolactin has more than 300 separate functions including affecting mammary growth, differentiation, secretion and anti-apoptosis. In the previous studies, prolactin induced Bcl-2 expression to prevent apoptosis and also provoked the activity of ornithine decarboxylase (ODC). Our previous data showed that ODC overexpression upregulates Bcl-2 and prevents tumor necrosis factor alpha (TNF-alpha)- and methotrexate (MTX)-induced apoptosis. Here, we further investigate whether prolactin prevents MTX-induced apoptosis through inducing ODC activity and the relationship between ODC and Bcl-2 upon prolactin stimulation. Prolactin prevented MTX-induced apoptosis in a dose-dependent manner in HL-60 cells. Following prolactin stimulation, ODC enzyme activity also shows an increase in a dose-dependent manner, expressing its maximum level at 3 h, and rapidly declining thereafter. Prolactin-induced ODC activity is completely blocked by a protein kinase C delta (PKCdelta) inhibitor, rottlerin. However, there are no changes in the expressions of ODC mRNA and protein level after prolactin stimulus. It indicates that prolactin may induce ODC activity through the PCKdelta pathway. Besides, Bcl-2 expresses within 1 h of prolactin treatment and this initiating effect of prolactin is not inhibited by alpha-difluoromethylornithine (DFMO). However, Bcl-2 is further enhanced following prolactin stimulation for 4 h and this enhancement is blocked by DFMO. Bcl-2 has no effect on ODC activity and protein levels, but ODC upregulates Bcl-2, which is inhibited by DFMO. Overall, there are two different forms of prolactin effect, it induces Bcl-2 primarily, and following this it stimulates ODC activity. Consequently induced ODC activity further enhances the expression of Bcl-2. The anti-apoptotic effect of prolactin is diminished by DFMO and recovered by putrescine. Obviously, ODC activity is one basis for the anti-apoptotic mechanisms of prolactin. A Bcl-2 inhibitor, HA14-1, together with DFMO, completely blocks the anti-apoptotic effects of prolactin. These results suggest that increasing ODC activity is another way of prolactin preventing MTX-induced apoptosis and that this induction of ODC activity enhances the expression of Bcl-2 strongly enough to bring about the anti-apoptotic function.

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“…No statistical significant change in protein distribution was found following BSO treatment in the presence of ␥-glutamyl cysteine. et al, 2000), phosphatidylinositol-3-kinase (Desiderio et al, 1998), ␤-actin (Onyia et al, 1994), cyclin D3 (Mann et al, 1997) and histidine decarboxylase (Hocker et al, 1996) have all previously been linked to PKC activation in a number of liver cell lines. Both the activity and expression of calbindin (Gagnon and Welsh, 1997), glutamine fructose-6-phosphate amidotransferase (James et al, 2001), prostaglandin H synthase (Duniec et al, 1991) and the tumour suppressor gene Rb (Yen et al, 1993), can be modulated through PKC-␣ and in the absence of apoptosis, active PKC-␣ can increase c-myc expression in vitro (Zhao and Day, 2001).…”

Section: Discussionmentioning

confidence: 96%

Glutathione depletion modulates gene expression in HepG2 cells via activation of protein kinase C alpha

White¹,

Spence²,

Chipman³

2005

Toxicology

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RETRACTED: Hepatocyte Growth Factor-Induced Expression of Ornithine Decarboxylase, c-met,and c-mycIs Differently Affected by Protein Kinase Inhibitors in Human Hepatoma Cells HepG2

Cited by 29 publications

References 40 publications

Hepatocyte growth factor regulates cyclooxygenase-2 expression via β-catenin, Akt, and p42/p44 MAPK in human bronchial epithelial cells

Hepatocyte growth factor regulates cyclooxygenase-2 expression via β-catenin, Akt, and p42/p44 MAPK in human bronchial epithelial cells

Increasing ornithine decarboxylase activity is another way of prolactin preventing methotrexate-induced apoptosis: Crosstalk between ODC and BCL-2

Glutathione depletion modulates gene expression in HepG2 cells via activation of protein kinase C alpha

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