期刊
CANCER LETTERS
卷 359, 期 2, 页码 299-306出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2015.01.037
关键词
sst5TMD4; Acromegaly; Invasion; Proliferation
类别
资金
- Junta de Andalucia [BIO-0139, CTS-1406, PI-639-2012]
- Ministerio de Economia y Competitividad, Gobierno de Espana [BFU2013-43282]
- Proyectos de Investigacion en Salud FIS, Instituto de Salud Carlos III [PI13-00651]
- CIBERobn
- Ayuda Merck Serono
- Department of Veterans Affairs
- Veterans Health Administration
- Office of Research and Development Merit Award
- National Institutes of Health [R21AG031465, R01 DK088133]
- [P09-CTS-5051]
- [CD11/00276]
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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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