β-arrestin 2 is required for dopamine receptor type 2 inhibitory effects on AKT phosphorylation and cell proliferation in pituitary tumors

2020 ◽  
Author(s):  
Federica Mangili ◽  
Elena Giardino ◽  
Donatella Treppiedi ◽  
Anna Maria Barbieri ◽  
Rosa Catalano ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Dopamine Receptor ◽  
Pituitary Tumors ◽  
Receptor Type ◽  
Inhibitory Effects ◽  
Akt Phosphorylation

scholarly journals SAT-312 Beta-Arrestin 2 Is Required for Dopamine Receptor Type 2 Inhibitory Effects on Akt Phosphorylation and Cell Proliferation in Pituitary Tumors

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Federica Mangili ◽  
Elena Giardino ◽  
Donatella Treppiedi ◽  
Anna Maria Barbieri ◽  
Rosa Catalano ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Dopamine Receptor ◽  
Pituitary Tumors ◽  
Receptor Type ◽  
Inhibitory Effects ◽  
Akt Phosphorylation ◽  
First Choice ◽  
Antimitotic Effect

Abstract Dopamine receptor type 2 (DRD2) agonists are the first-choice treatment for PRL-secreting pituitary tumors but are poorly effective in non-functioning pituitary neuroendocrine tumors (NF-PitNETs). DRD2 reduces AKT phosphorylation in lactotrophs, but no data are available in NF-PitNETs. DRD2 effects on AKT are mediated by a β-arrestin 2-dependent mechanism in mouse striatum. The aim of this study was to investigate DRD2 effects on AKT phosphorylation and cell proliferation in human primary cultured NF-PitNET cells and in rat tumoral lactotroph cells MMQ, and to test β-arrestin 2 involvement. We found that DRD2 agonist BIM53097 induced a reduction of p- AKT /total-AKT ratio in MMQ (-32.8±17.6%, p<0.001 vs basal) and in a subset (n=15/41,36.6%) of NF-PitNETs (subgroup 1). In the remaining NF-PitNETs (subgroup 2), BIM53097 induced an increase of p- AKT. The ability of BIM53097 to reduce p-AKT correlated to its antimitotic effect, since the majority of subgroup 1 NF-PitNETs was responsive to BIM53097 and nearly all subgroup 2 NF-PitNETs were resistant. β-arrestin2 was expressed in MMQ and in 80% of subgroup 1 NF-PitNETs, whereas it was undetectable in 77% of subgroup 2 NF-PitNETs. In MMQ, β-arrestin 2 silencing prevented DRD2 inhibitory effects on p-AKT and cell proliferation. Accordingly, β-arrestin 2 transfection in subgroup 2 NF-PitNETs conferred to BIM53097 the ability to inhibit both p-AKT and cell growth. In conclusion, we demonstrated that β-arrestin 2 is required for DRD2 inhibitory effects on AKT phosphorylation and cell proliferation in MMQ and NF-PitNETs, paving the way for a potential role of β-arrestin 2 as a biomarker predicting NF-PitNETs responsiveness to treatment with dopamine agonists.

scholarly journals Human non-functioning pituitary tumors invasiveness: inhibitory effects of dopamine receptor type 2 (DRD2) agonist and cofilin involvement

2016 ◽  
Author(s):  
Erika Peverelli ◽  
Elena Giardino ◽  
Donatella Treppiedi ◽  
Marco Locatelli ◽  
Valentina Vaira ◽  
...  
Keyword(s):  
Dopamine Receptor ◽  
Pituitary Tumors ◽  
Receptor Type ◽  
Inhibitory Effects

Dopamine receptor type 2 (DRD2) inhibits migration and invasion of human tumorous pituitary cells through ROCK-mediated cofilin inactivation

2016 ◽  
Vol 381 (2) ◽  
pp. 279-286 ◽  
Author(s):  
E. Peverelli ◽  
E. Giardino ◽  
D. Treppiedi ◽  
M. Locatelli ◽  
V. Vaira ◽  
...  
Keyword(s):  
Dopamine Receptor ◽  
Receptor Type ◽  
Migration And Invasion ◽  
Pituitary Cells

A Novel Variant in Dopamine Receptor Type 2 Gene is Associated with Schizophrenia

2020 ◽  
Author(s):  
Farina Hanif ◽  
Qurat-ul-Ain Amir ◽  
Washdev Washdev ◽  
Fareena Bilwani ◽  
Shabana Usman Simjee ◽  
...  
Keyword(s):  
Dopamine Receptor ◽  
Receptor Type ◽  
Novel Variant
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