The oncostatin M receptor/gp130 ligand murine oncostatin M induces apoptosis in adrenocortical Y-1 tumor cells

Auernhammer, Christoph J.; Dorn, Franziska; Vlotides, George; Hengge, Sabine; Kopp, Florian; Spoettl, Gerald; Cengic, Neziha; Engelhardt, D.; Weber, Matthias M.

doi:10.1677/joe.0.1800479

Cited by 13 publications

(8 citation statements)

References 17 publications

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“…Like the EGFR, it has established roles in promoting cancer and tumor formation in malignant prostate [42], lung, head and neck, and cervical [43] tissue. In addition, OSM has been shown in some cells to induce apoptosis [44–46]. Thus, stimulation of the OSM receptor was a logical candidate for testing our hypothesis that STAT3 is a mediator apoptosis, independent of EGFR activity.…”

Section: Resultsmentioning

confidence: 99%

EGFR-mediated apoptosis via STAT3

Jackson

Ceresa

2017

Experimental Cell Research

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The Epidermal Growth Factor Receptor (EGFR) is a cell surface receptor with primary implications in cell growth in both normal and malignant tissue. Paradoxically, cell lines that hyperexpress the EGFR have been documented to undergo receptor-mediated apoptosis. The underlying mechanism by which EGF-induced apoptosis occurs however remains inexplicit. In an attempt to identify this mechanism, we assessed downstream effectors of EGFR in MDA-MB-468 cells during conditions of EGF-induced apoptosis. The effector assessment revealed STAT3 as a potential mediator of EGF-induced apoptosis. Alternative strategies for activating STAT3, independent of EGFR stimulation, resulted in the induction of the apoptotic pathways. A reduction in STAT3 expression via RNAi resulted in a significant attenuation of EGF-induced PARP cleavage. Our findings support STAT3 as a positive mediator of EGF-induced apoptosis in MDA-MB-468 cells.

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Section: Resultsmentioning

confidence: 99%

EGFR-mediated apoptosis via STAT3

Jackson

Ceresa

2017

Experimental Cell Research

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“…Protein extraction and Western blotting were performed as described recently [26,27]. Briefly, cells were lysed in 500 µl lysis buffer.…”

Section: Methodsmentioning

confidence: 99%

The Novel mTOR Inhibitor RAD001 (Everolimus) Induces Antiproliferative Effects in Human Pancreatic Neuroendocrine Tumor Cells

et al. 2007

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Background/Aim: Tumors exhibiting constitutively activated PI(3)K/Akt/mTOR signaling are hypersensitive to mTOR inhibitors such as RAD001 (everolimus) which is presently being investigated in clinical phase II trials in various tumor entities, including neuroendocrine tumors (NETs). However, no preclinical data about the effects of RAD001 on NET cells have been published. In this study, we aimed to evaluate the effects of RAD001 on BON cells, a human pancreatic NET cell line that exhibits constitutively activated PI(3)K/Akt/mTOR signaling. Methods: BON cells were treated with different concentrations of RAD001 to analyze its effect on cell growth using proliferation assays. Apoptosis was examined by Western blot analysis of caspase-3/PARP cleavage and by FACS analysis of DNA fragmentation. Results: RAD001 potently inhibited BON cell growth in a dose-dependent manner which was dependent on the serum concentration in the medium. RAD001-induced growth inhibition involved G0/G1-phase arrest as well as induction of apoptosis. Conclusion: In summary, our data demonstrate antiproliferative and apoptotic effects of RAD001 in NET cells in vitro supporting its clinical use in current phase II trials in NET patients.

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“…Few studies focused on the effects of OSM on apoptosis, and the conclusions were opposite according to the model. A recent study has shown that OSM induces apoptosis in adrenocortical Y-1 tumor cell line, implicating the JAK-STAT pathway and caspase-3 activation (Auernhammer et al, 2004). On the other hand, OSM was able to protect MG63 osteosarcoma cells from apoptosis induced by an anti-Fas antibody by preventing the loss of Bcl-2 protein (Jilka et al, 1998).…”

Section: Introductionmentioning

confidence: 98%

Sensitization of osteosarcoma cells to apoptosis by oncostatin M depends on STAT5 and p53

et al. 2007

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Oncostatin M (OSM), a cytokine of the interleukin-6 family, induces growth arrest and differentiation of osteoblastic cells into glial-like/osteocytic cells. Here, we asked whether OSM regulates apoptosis of normal or transformed (osteosarcoma) osteoblasts. We show that OSM sensitizes cells to apoptosis induced by various death inducers such as staurosporine, ultraviolet or tumor necrosis factor-a. Apoptosis is mediated by the mitochondrial pathway, with release of cytochrome c from the mitochondria to the cytosol and activation of caspases-9 and -3. DNA micro-arrays revealed that OSM modulates the expression of Bax, Bad, Bnip3, Bcl-2 and Mcl-1. Pharmacological inhibitors, dominant-negative signal transducer and activator of transcriptions (STATs), stable RNA interference and knockout cells indicated that the transcription factors p53 and STAT5, which are activated by OSM, are implicated in the sensitization to apoptosis, being responsible for Bax induction and Bcl-2 reduction, respectively. These results indicate that, in addition to growth arrest and induced differentiation, OSM also sensitizes normal and transformed osteoblasts to apoptosis by a mechanism implicating (i) activation and nuclear translocation of STAT5 and p53 and (ii) an increased Bax/Bcl-2 ratio. Therefore, association of OSM with kinase inhibitors such as Sts represents new therapeutic opportunities for wild-type p53 osteosarcoma.

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The oncostatin M receptor/gp130 ligand murine oncostatin M induces apoptosis in adrenocortical Y-1 tumor cells

Cited by 13 publications

References 17 publications

EGFR-mediated apoptosis via STAT3

EGFR-mediated apoptosis via STAT3

The Novel mTOR Inhibitor RAD001 (Everolimus) Induces Antiproliferative Effects in Human Pancreatic Neuroendocrine Tumor Cells

Sensitization of osteosarcoma cells to apoptosis by oncostatin M depends on STAT5 and p53

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