Growth Hormone Receptor Blockade Inhibits Growth Hormone-Induced Chemoresistance by Restoring Cytotoxic-Induced Apoptosis in Breast Cancer Cells Independently of Estrogen Receptor Expression

Minoia, Mariella; Gentilin, Erica; Molè, Daniela; Rossi, Martina; Filieri, Carlo; Tagliati, Federico; Baroni, Alessandra; Ambrosio, Maria Rosaria; Uberti, Ettore C. degli; Zatelli, Maria Chiara

doi:10.1210/jc.2011-3340

Cited by 40 publications

(30 citation statements)

References 33 publications

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“…To the present, GH-induced JNK phosphorylation has been demonstrated in macrophages [34], in NIH 3 T3 fibroblasts [33], and also in chinese hamster ovary cells stably transfected with rat GH receptor cDNA [51]. However, GH has been shown to reduce both basal and doxorubicin-stimulated JNK transcriptional activity and phosphorylation in both MDA-MB-231 and MCF7 cells [52], thus demonstrating the complexity of GH-mediated JNK regulation.…”

Section: Discussionmentioning

confidence: 99%

Growth hormone pathways signaling for cell proliferation and survival in hippocampal neural precursors from postnatal mice

et al. 2014

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BackgroundAccumulating evidence suggests that growth hormone (GH) may play a major role in the regulation of postnatal neurogenesis, thus supporting the possibility that it may be also involved in promoting brain repair after brain injury. In order to gain further insight on this possibility, in this study we have investigated the pathways signaling the effect of GH treatment on the proliferation and survival of hippocampal subgranular zone (SGZ)-derived neurospheres.ResultsOur results demonstrate that GH treatment promotes both proliferation and survival of SGZ neurospheres. By using specific chemical inhibitors we have been also able to demonstrate that GH treatment promotes the activation of both Akt-mTOR and JNK signaling pathways, while blockade of these pathways either reduces or abolishes the GH effects. In contrast, no effect of GH on the activation of the Ras-ERK pathway was observed after GH treatment, despite blockade of this signaling path also resulted in a significant reduction of GH effects. Interestingly, SGZ cells were also capable of producing GH, and blockade of endogenous GH also resulted in a decrease in the proliferation and survival of SGZ neurospheres.ConclusionsAltogether, our findings suggest that GH treatment may promote the proliferation and survival of neural progenitors. This effect may be elicited by cooperating with locally-produced GH in order to increase the response of neural progenitors to adequate stimuli. On this view, the possibility of using GH treatment to promote neurogenesis and cell survival in some acquired neural injuries may be envisaged.

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Section: Discussionmentioning

confidence: 99%

Growth hormone pathways signaling for cell proliferation and survival in hippocampal neural precursors from postnatal mice

et al. 2014

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“…Zatelli's group also demonstrated a protective effect of GH in inhibiting doxorubicin induced apoptosis in estrogen-receptor negative breast cancer cells, which was significantly abrogated using Pegvisomant (182). In an in vitro study, Lobie and colleagues had identified autocrine GH causing increased resistance of breast cancer cells (MCF7, T47D, and MDA-MB-231) to mitomycin-C (MMC)-induced apoptosis by protecting against DNA-damage(160).…”

Section: Role Of Gh-ghr In Cancer Therapy Resistancementioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Lessons from growth hormone receptor gene-disrupted mice: are there benefits of endocrine defects?

Basu

Qian

Kopchick

2018

European Journal of Endocrinology

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Growth hormone (GH) is produced primarily by anterior pituitary somatotroph cells. Numerous acute human (h) GH treatment and long-term follow-up studies and extensive use of animal models of GH action have shaped the body of GH research over the past 40-50 years. Work on the GH receptor (R) knock-out (GHRKO) mice and results of studies on GH resistant Laron Syndrome (LS) patients have helped define many physiological actions of GH including those dealing with metabolism, obesity, cancer, diabetes, cognition, and aging/longevity. In this review, we have discussed several issues dealing with these biological effects of GH and attempt to answer the question of whether decreased GH action may be beneficial.

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“…The NCI-H727 and NCI-H720 cells were treated with 100 nM everolimus or NVP-BEZ235 for 72 h. Vehicle-treated cells served as the controls. At the end of the incubation period, the cells were washed with PBS and incubated with 1 ml of staining solution (5 mg/ml propidium iodide, 10 mg/ml and analyzed using the FloMax Software (Partec), as described previously (Minoia et al 2012).…”

Section: Flow Cytometrymentioning

confidence: 99%

mTOR, p70S6K, AKT, and ERK1/2 levels predict sensitivity to mTOR and PI3K/mTOR inhibitors in human bronchial carcinoids

Gagliano¹,

Bellio²,

Gentilin³

et al. 2013

Endocrine-Related Cancer

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Bronchial carcinoids (BCs) are rare neuroendocrine tumors that are still orphans of medical treatment. Human BC primary cultures may display resistance to everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), in terms of cell viability reduction. Our aim was to assess whether the novel dual phosphatidylinositol 3-kinase (PI3K)/mTOR inhibitor NVP-BEZ235 is effective in everolimus-resistant human BC tissues and cell lines. In addition, we searched for possible markers of the efficacy of mTOR inhibitors that may help in identifying the patients who may benefit from treatment with mTOR inhibitors, sparing them from ineffective therapy. We found that NVP-BEZ235 is twice as potent as everolimus in reducing cell viability and activating apoptosis in human BC tissues that display sensitivity to mTOR inhibitors, but is not effective in everolimus-resistant BC tissues and cell lines that bypass cyclin D1 downregulation and escape G0/G1 blockade. Rebound AKT activation was not observed in response to treatment with either mTOR inhibitor in the 'resistant' BC cells. In addition to total mTOR levels, putative markers of the sensitivity of BCs to mTOR inhibitors are represented by AKT, p70S6K (RPS6KB2), and ERK1/2 (MAPK3/1) protein levels. Finally, we validated these markers in an independent BC group. These data indicate that the dual PI3K/mTOR inhibitor NVP-BEZ235 is more potent than everolimus in reducing the proliferation of human BC cells. 'Resistant' cells display lower levels of mTOR, p70S6K, AKT, and ERK1/2, indicating that these proteins may be useful as predictive markers of resistance to mTOR and PI3K/mTOR inhibitors in human BCs.

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Growth Hormone Receptor Blockade Inhibits Growth Hormone-Induced Chemoresistance by Restoring Cytotoxic-Induced Apoptosis in Breast Cancer Cells Independently of Estrogen Receptor Expression

Cited by 40 publications

References 33 publications

Growth hormone pathways signaling for cell proliferation and survival in hippocampal neural precursors from postnatal mice

Growth hormone pathways signaling for cell proliferation and survival in hippocampal neural precursors from postnatal mice

MECHANISMS IN ENDOCRINOLOGY: Lessons from growth hormone receptor gene-disrupted mice: are there benefits of endocrine defects?

mTOR, p70S6K, AKT, and ERK1/2 levels predict sensitivity to mTOR and PI3K/mTOR inhibitors in human bronchial carcinoids

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