We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
HGF/c-met system targeting PI3K/AKT and STAT3/phosphorylated-STAT3 pathways in pituitary adenomas: an immunohistochemical characterization in view of targeted therapies.
- Authors
Trovato, Maria; Torre, Maria Luisa; Ragonese, Marta; Simone, Angela; Scarfì, Rosy; Barresi, Valeria; Giuffrè, Giuseppe; Benvenga, Salvatore; Angileri, Flavio F.; Tuccari, Giovanni; Trimarchi, Francesco; Ruggeri, Rosaria Maddalena; Cannavò, Salvatore
- Abstract
The ligand/receptor hepatocyte growth factor (HGF)/c-met signaling system promotes cellular growth and angiogenesis through PI3K/phosphor-Akt and STAT3/phosphor-STAT3 downstream effectors. In this study, we have evaluated the expression of molecules of the HGF/c-met pathway in pituitary adenomas (PA). The expression of HGF, c-met, PI3K (p85αsubunit) pAkt, STAT3, and pSTAT3 was analyzed by immunohistochemistry in an archival series of 30 PA (12 non-functioning and 18 functioning; 25 macroadenomas and 5 microadenomas). PAs expressed all six proteins in tumor epithelial cells. The proportion of c-met +ve cells was greater than HGF +ve cells (49 ± 19 vs 34 ± 17 %, P < 0.01), the pAkt +ve cells greater than PI3K +ve cells (39 ± 16.0 vs 1.3 ± 0.5 %, P < 0.001), and the STAT3 +ve cells greater than active pSTAT3 +ve cells (14 ± 8 vs 7 ± 6 %, P < 0.01). Furthermore, endothelial Akt immunostaining was detected on the vascular surface area of 17 PAs, in macroadenomas more frequently than in microadenomas (82 vs 18 %). The percentage of immunostained endothelial cells was greater in macro than in microadenomas (19 ± 7 and 7 ± 3 %; P < 0.05). In conclusion, HGF and c-met are widely expressed in PA, and correlate with pAkt expression. These data, together with the finding of pAkt immunostaining on microvascular areas related to tumor size, suggest a major role of the pAKT signaling in tumor growth and angiogenesis. There might be practical implications for the targeted therapy of PA.
- Subjects
GENE targeting; PHOSPHORYLATION; ADENOMA; CELLULAR signal transduction; IMMUNOHISTOCHEMISTRY; TUMOR growth; DISEASE risk factors
- Publication
Endocrine (1355008X), 2013, Vol 44, Issue 3, p735
- ISSN
1355-008X
- Publication type
Article
- DOI
10.1007/s12020-013-9950-x