Alpha2-adrenoceptor agonists trigger prolactin signaling in breast cancer cells

Castillo, Luciana Andrea; Rivero, Ezequiel Mariano; Goffin, Vincent; Lüthy, Isabel Alicia

doi:10.1016/j.cellsig.2017.03.003

Cited by 26 publications

(26 citation statements)

References 51 publications

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“…We have previously described low expression of α 2A ‐adrenoceptor in several human breast cancer cell lines . For example, the human breast cancer cell MCF‐7 expressed nearly 200 times more ADRA2C than ADRA2A . Altogether, these results suggest that the proliferation‐enhancing effect we have described for clonidine and dexmedetomidine, both nonspecific α 2 ‐adrenergic agonists used in clinics in the context of anaesthesia, could be mediated almost exclusively by the α 2C subtype.…”

Section: Discussionsupporting

confidence: 58%

“…A recent study has also shown that perioperative use of dexmedetomidine increases the metastatic burden of a mammary adenocarcinoma in rats, Lewis lung carcinoma in C57BL/6 mice, and colon adenocarcinoma in BALB/c mice . Rauwolscine, an α 2 ‐adrenergic antagonist that we proved to be a strong inhibitor of breast tumour growth, has a higher affinity for the α 2C subtype…”

Section: Discussionmentioning

confidence: 66%

“…21,44 For example, the human breast cancer cell MCF-7 expressed nearly 200 times more ADRA2C than ADRA2A. 44 Altogether, these results suggest that the proliferation-enhancing effect we have described for clonidine and dexmedetomidine, 15,19,44 both nonspecific α 2 -adrenergic agonists used in clinics in the context of anaesthesia, 45 could be mediated almost exclusively by the α 2C subtype. A recent study has also shown that perioperative use of dexmedetomidine increases the metastatic burden of a mammary adenocarcinoma in rats, Lewis lung carcinoma in C57BL/6 mice, and colon adenocarcinoma in BALB/c mice.…”

Section: Discussionmentioning

confidence: 71%

“…On the contrary, in cell lines the expression of ADRA2A was extremely low. We have previously described low expression of α 2A ‐adrenoceptor in several human breast cancer cell lines . For example, the human breast cancer cell MCF‐7 expressed nearly 200 times more ADRA2C than ADRA2A .…”

Section: Discussionmentioning

confidence: 99%

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Prognostic significance of α‐ and β2‐adrenoceptor gene expression in breast cancer patients

Rivero

Martinez

Bruque

et al. 2019

Brit J Clinical Pharma

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Aims Breast cancer is the most frequently diagnosed and leading cause of cancer death among women worldwide. It was classified within molecular intrinsic subtypes: luminal A, luminal B, human epidermal growth factor receptor 2‐enriched and basal‐like. Epinephrine and norepinephrine, released during stress, bind to adrenoceptors. α2‐adrenoceptors are encoded by the ADRA2A, ADRA2B and ADRA2C genes and β2 by ADRB2. Methods We compiled several publicly available Affymetrix gene expression datasets, obtaining a large cohort of 1924 patients with distant metastasis‐free survival (DMFS) data and evaluated the association between adrenoceptor expression, clinicopathological markers and outcome. Results ADRA2A high expressing tumours also expressed hormone receptors and presented diminished tumour size, grade and not compromised lymph nodes. ADRB2 high expression was found in smaller, low grade, oestrogen receptor‐positive tumours. Both were significantly associated with the absence of metastasis. High expression of ADRA2C was positively associated with increased tumour size and metastatic relapse. We observed a significant increase in DMFS of patients with high ADRA2A (hazard ratio 0.54, 95% CI 0.45–0.65, P < .001) and ADRB2 (0.77, 0.64–0.93, P = .006) expression and a decrease with ADRA2C high expression (1.45, 1.16–1.81, P = .001). For patients with luminal tumours, ADRA2A was the only factor that retained its significance as an independent predictor of DMFS while ADRA2C expression was an independent predictor for worse prognosis in basal‐like tumours. Conclusions We herein provide new insight for a potential role of ADRA2A and ADRA2C in breast cancer. In low‐ and medium‐income countries, their incorporation to routine immunohistochemistry analysis of biopsies or tumour samples, could provide additional low‐cost prognostic factors.

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Prognostic significance of α‐ and β2‐adrenoceptor gene expression in breast cancer patients

Rivero

Martinez

Bruque

et al. 2019

Brit J Clinical Pharma

Self Cite

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“…Cells were incubated in DMEM without FCS containing PRLR antagonist Δ1–9-G129R-hPRL (5 µg/mL) at different time points, which were selected based on previous reports [26-28, 30] and a time-course analysis performed in a preliminary experiment (data not shown). For total ERK (t-ERK), phospho-ERK (p-ERK), total AKT (t-AKT), and phospho-Akt (p-Akt) determination, or Bax and Bcl-2 expression, total proteins were extracted with lysis buffer containing protease inhibitor cocktail and phosphatase inhibitors (NaF 10 mM, Na-orthovanadate 2 mM, β-glycerol phosphate 80 mM) and protease inhibitor kit (Sigma).…”

Section: Methodsmentioning

confidence: 99%

JAK2/STAT5 Pathway Mediates Prolactin-Induced Apoptosis of Lactotropes

et al. 2018

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Prolactinomas are increasingly viewed as a “problem of signal transduction.” Consequently, the identification of factors and signaling pathways that control lactotrope cell turnover is needed in order to encourage new therapeutic developments. We have previously shown that prolactin (PRL) acts as a proapoptotic and antiproliferative factor on lactotropes, maintaining anterior pituitary cell homeostasis, which contrasts with the classical antiapoptotic and/or proliferative actions exerted by PRL in most other target tissues. We aimed to investigate the PRLR-triggered signaling pathways mediating these nonclassical effects of PRL in the pituitary. Our results suggest that (i) the PRLR/Jak2/STAT5 pathway is constitutively active in GH3 cells and contributes to PRL-induced apoptosis by increasing the Bax/Bcl-2 ratio, (ii) PRL inhibits ERK1/2 and Akt phosphorylation, thereby contributing to its proapoptotic effect, and (iii) the PI3K/Akt pathway participates in the PRL-mediated control of lactotrope proliferation. We hypothesize that the alteration of PRL actions in lactotrope homeostasis due to the dysregulation of any of the mechanisms of actions described above may contribute to the pathogenesis of prolactinomas.

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Effects of dexmedetomidine on glioma cells in the presence or absence of cisplatin

Yang

Chen

Yan

et al. 2019

J of Cellular Biochemistry

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With the extensive use of dexmedetomidine (Dex) in the surgical resection of tumours for its potent sedative and analgesic properties, its effects on various properties of tumours have received increased attention. The study described herein aimed to investigate the effects of Dex on glioma cells in the presence or absence of cisplatin (DDP). Glioma U251 and U87MG cells were treated with different doses (1‐50 nM) of Dex for 12 hours, then recultured in a Dex‐free medium. In addition, Dex was added to U251 and U87MG cells 12 hours before or simultaneously with a 12‐hour DDP treatment. Treatment with Dex increased the viability of both cell lines; this effect continued for at least 24 hours after Dex was removed. A cell invasion assay indicated that Dex inhibited cell invasion at 50 nM, but not at 10 nM. Western blot analysis showed that Dex increased the expression of phosphorylated extracellular‐signal‐regulated kinase 1/2, phosphoitide 3‐kinase and p‐AKT, but decreased ROCK protein levels at a dose of 50 nM. Intracellular Ca 2+ concentration was decreased by Dex in a dose‐dependent manner. DDP toxicity was attenuated by 10 nM Dex added either before or with DDP treatment. However, pretreatment with 50 nM Dex instead enhanced the toxicity of DDP. Single‐dose treatment with Dex did not significantly change glioma volume in nude mice, but changed the expression of Ki67 and matrix metalloproteinase‐3 in the tumour. In conclusion, this study provides evidence of the regulatory effects of Dex on proliferation, invasion and chemosensitivity of glioma cells, and outlines potential mechanisms for these effects.

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Alpha2-adrenoceptor agonists trigger prolactin signaling in breast cancer cells

Cited by 26 publications

References 51 publications

Prognostic significance of α‐ and β2‐adrenoceptor gene expression in breast cancer patients

Prognostic significance of α‐ and β2‐adrenoceptor gene expression in breast cancer patients

JAK2/STAT5 Pathway Mediates Prolactin-Induced Apoptosis of Lactotropes

Effects of dexmedetomidine on glioma cells in the presence or absence of cisplatin

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