当前位置： SCI文献检索 > CANCER LETTERS期刊下所有文献 > Truncated somatostatin receptor variant sst5TMD4 confers aggressive features (proliferation, invasion and reduced octreotide response) to somatotropinomas.

Truncated somatostatin receptor variant sst5TMD4 confers aggressive features (proliferation, invasion and reduced octreotide response) to somatotropinomas.

Abstract：

:The GH/IGF1 response of somatotropinomas to somatostatin analogues (SSA) is associated with their pattern of somatostatin receptor (sst1-sst5) expression. Recently, we demonstrated that expression of a truncated sst5-variant (sst5TMD4) can influence the secretory response of somatotropinomas to SSA-therapy; however, its potential relationship with aggressive features (e.g. invasion/proliferation) is still unknown. Here, we show that sst5TMD4 is present in 50% of non-functioning pituitary-adenomas (NFPA) (n = 30) and 89% of somatotropinomas (n = 36), its expression levels being highest in somatotropinomas > > NFPAs > > > normal pituitaries (negligible expression; n = 8). In somatotropinomas, sst5TMD4 mRNA and protein levels correlated positively, and its expression was directly associated with tumor invasiveness (cavernous/sphenoid sinus), and inversely correlated with age and GH/IGF1 reduction after 3-6 months with octreotide-LAR therapy. GNAS+ somatotropinomas expressed lower sst5TMD4 levels. ROC analysis revealed sst5TMD4 expression as the only marker, within all sst-subtypes, capable to predict tumor invasiveness in somatotropinomas. sst5TMD4 overexpression increased cell viability in cultured somatotropinoma (n = 5). Hence, presence of sst5TMD4 associates with increased aggressive features and worse prognosis in somatotropinomas, thereby providing a potentially useful tool to refine somatotropinoma diagnosis, predict outcome of clinical response to SSA-therapy and develop new therapeutic targets.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Luque RM,Ibáñez-Costa A,Neto LV,Taboada GF,Hormaechea-Agulla D,Kasuki L,Venegas-Moreno E,Moreno-Carazo A,Gálvez MÁ,Soto-Moreno A,Kineman RD,Culler MD,Gahete MD,Gadelha MR,Castaño JP

doi

10.1016/j.canlet.2015.01.037

subject

Has Abstract

pub_date

2015-04-10 00:00:00

pages

299-306

issue

2

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(15)00071-3

journal_volume

359

pub_type

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