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Updated: Jun 24, 2026
Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
Published on: July 17, 2020
Tumoral prostate shows different expression pattern of somatostatin receptor 2 (SSTR2) and phosphotyrosine
Ariel Ernesto Cariaga-Martinez1, María Angelica Lorenzati, Mario Alejandro Riera
1Laboratorio de Biologia Molecular, Facultad de Ciencias Exactas Aplicada Químicas y Naturales, Universidad Nacional de Misiones, N3300LQH Posadas, Argentina.
Abstract:
Prostate proliferation is dependent of androgens and many peptide hormones. Recent reports suggest that SSTR2 and SHP-1 were two fundamental components on antiproliferative effect of somatostatin. Many studies on SHP-1 revealed that the expression of this protein was diminished or abolished in several of the cancer cell lines and tissues examined. However, it is necessary to confront the cell lines data with real situation in cancer cases. Our studies have shown that epithelial expressions of both proteins, SHP-1 and SSTR2, in normal and benign hyperplasia are localized in the luminal side of duct and acinar cells. Also, SSTR2 is expressed in stromal cells. In malignant prostate tissue, SHP-1 was diminished in 28/45 cases or absent in 12/45 cases, whereas SSTR2 epithelial was diminished in 38/45 cases or lost in only 2/45 cases. The intensity of immunostained was highly negative correlated with Gleason grade for two proteins.
Insights
Prostate cancer cell proliferation is linked to somatostatin receptor 2 (SSTR2) and SHP-1 protein expression. Reduced levels of these proteins correlate with higher Gleason grades in prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Urology
Background:
- Prostate proliferation is influenced by androgens and peptide hormones.
- Somatostatin receptor 2 (SSTR2) and SHP-1 are key in somatostatin's antiproliferative effects.
- Previous studies indicated diminished SHP-1 in cancer cell lines, necessitating validation in clinical prostate cancer tissues.
Purpose of the Study:
- To investigate the expression patterns of SSTR2 and SHP-1 in normal, benign hyperplastic, and malignant prostate tissues.
- To correlate the expression levels of SSTR2 and SHP-1 with prostate cancer Gleason grade.
Main Methods:
- Immunohistochemical analysis of SSTR2 and SHP-1 expression in prostate tissue samples.
- Quantitative assessment of protein expression intensity.
- Statistical correlation analysis between protein expression and Gleason grade.
Main Results:
- In normal and benign prostate tissues, SSTR2 and SHP-1 were localized to the luminal side of ductal and acinar cells; SSTR2 was also found in stromal cells.
- In malignant prostate tissues, SHP-1 was diminished in 62% (28/45) and absent in 27% (12/45) of cases.
- SSTR2 epithelial expression was diminished in 84% (38/45) and lost in only 4% (2/45) of malignant cases.
- A significant negative correlation was observed between the intensity of SSTR2 and SHP-1 immunostaining and the Gleason grade.
Conclusions:
- Both SSTR2 and SHP-1 expression are significantly reduced in prostate cancer, with a notable decrease in SSTR2 epithelial expression.
- The diminished expression of SSTR2 and SHP-1 correlates negatively with prostate cancer aggressiveness (Gleason grade).
- These findings highlight the potential role of SSTR2 and SHP-1 as biomarkers for prostate cancer progression.
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