Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroendocrine cells are thought to have a regulatory role in prostatic epithelial growth and may be prognostically useful in prostatic adenocarcinoma. To determine the extent of neuroendocrine differentiation in high-grade prostatic intraepithelial neoplasia (PIN), a putative precursor of cancer, we studied the immunohistochemical expression of 10 markers in 26 radical prostatectomy specimens with PIN and adenocarcinoma. Expression was measured as mean percent of positive cases and positive high-power (x40) fields. The highest percentage of cases showed immunoreactivity for serotonin (73%, PIN; 54%, carcinoma), neuron-specific enolase (NSE) (67%, PIN; 46%, carcinoma), chromogranin (62%, PIN; 65%, carcinoma), and human chorionic gonadotropin (hCG) (30%, PIN; 22%, carcinoma); the remaining markers showed immunoreactivity in fewer than 5% of cases (somatostatin, calcitonin, corticotropin) or in no cases (thyrotropin, prolactin, and glucagon). At least one of the markers was present in 88% of cases of PIN and 92% of carcinoma. Non-neoplastic epithelial cells expressed serotonin, NSE, chromogranin, and hCG in every case, and the expression was significantly greater than in PIN and cancer. Stepwise regression analysis revealed the following positive correlations: chromogranin expression in PIN and patient age, NSE expression in cancer and number of lymph node metastases, and hCG expression in cancer and percentage of Gleason pattern 5; serotonin expression in PIN and cancer did not correlate with any of the clinical and pathologic factors. Neuroendocrine differentiation is downregulated in prostatic carcinogenesis, with intermediate levels of expression in PIN compared with normal cells and carcinoma.
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PMID:Neuroendocrine differentiation in prostatic intraepithelial neoplasia and adenocarcinoma. 797 47

The present study was intended to gain additional information on the growth regulation of prostate by somatostatin (SRIF) and the intracellular events involved. The human prostate adenocarcinoma cell lines PC-3 and LNCaP produce SRIF and express subtypes 2 and 5 of SRIF receptors. The secretion of SRIF is related to the proliferative status of these cells; an inverse relationship exists between cell proliferation and the amount of secreted SRIF. Moreover, the growth of PC-3 cells is inhibited by SRIF overexpression and increased by blockage of endogenous SRIF. Coincident with the increase in SRIF secretion, the activity and levels of the SH2 domain containing protein tyrosine phosphatase (SHP)-1, present in PC-3 cells are augmented, but the effect can be partially prevented by neutralization of secreted endogenously SRIF. The activity of SHP-1 is also stimulated by the SRIF analog RC160. Overexpression of SHP-1 induces inhibition of PC-3 cell growth. SHP-1 is also present in normal prostate, benign prostatic hyperplasia, prostatic intraepithelial neoplasia, and well differentiated adenocarcinoma. In contrast, no signal is detected in poorly differentiated prostate cancer. These findings demonstrate that SRIF inhibits PC-3 and LNCaP cell proliferation through an autocrine/paracrine SRIF loop. This effect could be mediated by activation of the tyrosine phosphatase SHP-1 detected in these cells as well as in human prostate and prostate cancer.
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PMID:Autocrine regulation of human prostate carcinoma cell proliferation by somatostatin through the modulation of the SH2 domain containing protein tyrosine phosphatase (SHP)-1. 1183 42

The aim of the study is to examine the tissue expression and localization of the somatostatin receptors (SSTRs) in prostate cancer (PCa) with neuroendocrine (NE) differentiation. The five SSTR subtypes (SSTR1 to 5) were evaluated immunohistochemically in the secretory cells of normal-looking epithelium (Nep), high-grade prostatic intraepithelial neoplasia (HGPIN) and PCa in 20 radical prostatectomies (RPs) with Gleason score 3+3=6 acinar PCa; 20 RPs with GS 4+4=8 and 4+5=9 PCa; and 20 RPs with PCa with NE differentiation. The basal cells were evaluated in Nep and HGPIN. In all groups the stromal smooth muscle and endothelial cells were also analyzed. Concerning the secretory cells, (i) the greatest mean proportions of cells with strong cytoplasmic staining in PCa were seen for SSTR2, mainly in the group of RP with NE differentiation, and for SSTR4 in all three groups; the mean values in HGPIN were intermediate between Nep and PCa; (ii) Membrane staining was seen for SSTR3 and SSTR4; the mean percentages of positive cells, higher in SSTR3 than in SSTR4, decreased from Nep to HGPIN and PCa in all three RP groups; in the latter two, the mean percentages were similar; and (iii) Nuclear staining was seen with SSTR4 and SSTR5; for SSTR4, the mean percentages in the PCa of the three groups were higher than in HGPIN and Nep, the highest proportion being with PCa with NE differentiation. Concerning the basal cells, in Nep the mean proportions of cells with strong staining intensity were greater for SSTR1 and SSTR3 than for the other subtypes, the lowest being with SSTR2; in HGPIN the highest mean propositions of positive cells was with SSTR3, the proportions in the three RP groups being similar. Concerning the stromal smooth muscle and endothelial cells, the highest mean values being in SSTR1 and the lowest in SSTR5; for the former subtype the highest proportion of endothelial cells with strong intensity was seen in the RP NE group. In conclusion, this immunohistochemical study expands our knowledge on the expression and localization of five SSTRs in the various tissue components in the prostate with PCa with NE differentiation, compared with conventional PCa. Typing somatostatin receptor expression in NE tumours could be of relevance to target somatostatin analogue-based diagnostic approach and treatment.
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PMID:Immunohistochemical expression and localization of somatostatin receptor subtypes in prostate cancer with neuroendocrine differentiation. 2064 46

Data on the immunohistochemical expression and localization of the five somatostatin receptors (SSTRs) have been obtained by our group in separate studies concerning the many faces of prostate cancer (PCa), its precursor high grade prostatic intraepithelial neoplasia (HGPIN) and normal epithelium (Nep). This publication highlights the key findings, with special reference to: normal prostate epithelium; untreated HGPIN and PCa, both clinically and incidentally detected; PCa with NE differentiation; HGPIN and PCa following complete androgen ablation (CAA); and hormone refractory (HR) PCa. Taken together, the data obtained in these investigations demonstrate that SSTR profiling in individual patients with HGPIN and the multifaceted PCa is feasible and is of relevance to better tailor the somatostatin analogue-based treatment.
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PMID:Immunohistochemical expression and localization of somatostatin receptors in normal prostate, high grade prostatic intraepithelial neoplasia and prostate cancer and its many faces. 2282 45