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

A novel pathway activated by somatostatin receptor type 2 (SST2): Inhibition of pituitary tumor cell migration and invasion through cytoskeleton protein recruitment

“…Transwell assays were performed as previously described . Briefly, 300,000 cells/insert were plated in 24‐well inserts with pore diameter of 8 μm (Merck Millipore, Darmstadt, Germany) and incubated for 24 hr at 37°C in serum‐free medium with the indicated stimuli (BIM23120, octreotide, pasireotide, Y27632).…”

“…Cells were incubated for 10 min with or without BIM23120 (10 nM or 1 μm, as indicated). Dihydrochloride ROCK inhibitor Y27632 was used at 2.5 μM and cells were pre‐treated for 30 min . Total proteins were extracted from cultured cells or GH‐secreting tumor tissues ( n = 10), quantified by BCA assay, separated on SDS/polyacrylamide gels and transferred to a nitrocellulose filter.…”

“…Expression vectors coding for wild‐type or mutated S3D and S3A cofilin fused to GFP were previously described . FLNA fragments containing repeats 17–18, 19–20 or 21–24 fused to dsRed were described by Peverelli et al .…”

“…5 Alterations in the cofilin pathway have been correlated with invasiveness in different tumors, [6][7][8][9][10][11] including non-functioning pituitary tumors (NFPTs). 12 Moreover, in NFPTs dopamine (DA) receptor type 2 (DRD2) inhibited cells migration and invasion by increasing cofilin phosphorylation. 12 The main pharmacological target of GH-secreting pituitary tumors is the SS receptor type 2 (SST2), and long acting SS analogs reduce tumor growth and GH secretion in about 2/3 of patients.…”

Análise da expressão da filamina A nos tumores hipofisários e suas implicações clínicas e terapêuticas

“…Outros elementos do citoesqueleto celular têm sido implicados na invasividade de tumores hipofisários. Peverelli et al (184) descreveram que a menor expressão da cofilina, outra proteína que se liga à actina e participa de sua polimerização, correlacionou-se à invasividade em ACNF, e que sua perda de função, após fosforilação por ação de AD, pode estar envolvida no mecanismo da redução tumoral com o tratamento medicamentoso. Outros autores demonstraram que a expressão da fascina (FSCN1) se correlacionou à invasividade de tumores de hipófise e que a redução dessa proteína promove redução da ativação dos níveis de Notch 1 (185) .…”