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HGF/c-met system targeting PI3K/AKT and STAT3/phosphorylated-STAT3 pathways in pituitary adenomas: an immunohistochemical characterization in view of targeted therapies.
- Source :
-
Endocrine [Endocrine] 2013 Dec; Vol. 44 (3), pp. 735-43. Date of Electronic Publication: 2013 Apr 11. - Publication Year :
- 2013
-
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 :
- Adolescent
Adult
Aged
Endothelial Cells metabolism
Female
Humans
Immunohistochemistry
Male
Middle Aged
Phosphorylation
Adenoma metabolism
Hepatocyte Growth Factor metabolism
Phosphatidylinositol 3-Kinases metabolism
Pituitary Neoplasms metabolism
Proto-Oncogene Proteins c-akt metabolism
Proto-Oncogene Proteins c-met metabolism
STAT3 Transcription Factor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1559-0100
- Volume :
- 44
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Endocrine
- Publication Type :
- Academic Journal
- Accession number :
- 23576023
- Full Text :
- https://doi.org/10.1007/s12020-013-9950-x