Measurement of somatostatin receptor subtype 2 mRNA in breast cancer and corresponding normal tissue.

Abstract

Somatostatin analogs are effective in inhibiting growth of human breast cancer cell lines. These antiproliferative effects are mediated by specific receptors located on cell membranes. The somatostatin receptor subtype 2 (sst2) is the principal mediator of somatostatin effects in normal and cancer cells, and its presence has already been demonstrated in breast cancer. The purpose of our study was to evaluate the clinical relevance of the expression of sst2 by quantifying its mRNA in a large group of infiltrating breast cancers and their corresponding normal tissues.The expression of sst2 mRNA was measured with quantitative real time RT-PCR in 169 breast cancers and in their corresponding unaffected tissues. We evaluated the association of sst2 expression with the commonest clinical-pathologic features of breast cancer. The correlation with a marker of cell proliferation (Ki-67) and with receptor concentration was also evaluated.In cancer tissues, we found that the absolute concentrations of sst2 mRNA were significantly higher in estrogen receptor (ER)-positive samples ðP ¼ 0:002Þ as well as in lymph-node-negative cancers ðP ¼ 0:04Þ (Student's t-test or one-way ANOVA). In addition, sst2 mRNA was significantly higher in breast cancers than in corresponding unaffected tissues ðP ¼ 0:0002Þ. However, when the clinicalpathologic parameters were considered, this gradient maintained its statistical significance only in tumors expressing positive prognostic markers, such as the presence of ER ðP ¼ 0:0005Þ and progesterone receptors (PgR) ðP ¼ 0005Þ, and the lack of lymph-node involvement ðP ¼ 0:0003Þ. The same difference was also significant in postmenopausal women ðP ¼ 0:001Þ and in T1 patients ðP ¼ 0:001Þ. In addition, sst2 mRNA expression was significantly higher ðP ¼ 0:008Þ in lowproliferating breast cancers. Finally, we found that the quantitative expression of sst2 mRNA was directly related to the PgR concentration in breast cancer tissues ðP < 0:001Þ.Our data seem to indicate that an upregulation of sst2 gene expression is a common feature of breast cancers which, on the basis of conventional predictive parameters, are expected to have a better prognosis. Featuring a possible role of somatostatin analogs in combined endocrine therapies for breast cancer, our results seem to confirm that the sst2 status of the tumor should be previously investigated.

The new truncated somatostatin receptor variant sst5TMD4 is associated to poor prognosis in breast cancer and increases malignancy in MCF-7 cells

“…In line with previous studies showing that breast tumors express ssts, especially sst2 (Schulz et al, 1998;Orlando et al, 2004), this latter receptor was frequently and abundantly expressed in the samples examined herein. In contrast, our results provide the first evidence that the newly identified truncated variant sst5TMD4, which is absent in normal mammary gland tissue, is present in human breast cancer, namely in roughly one third of the poorly differentiated grade 3 tumors analyzed.…”

“…Specifically, 50-70% of breast tumors are positive for ssts (van Eijck et al, 1994) being sst2, overall, the most frequently and abundantly expressed in tumor cells (Orlando et al, 2004). Indeed, sst2 is considered a good prognosis factor due to its association with low proliferative and invasive breast cancers (Orlando et al, 2004).…”

“…Specifically, 50-70% of breast tumors are positive for ssts (van Eijck et al, 1994) being sst2, overall, the most frequently and abundantly expressed in tumor cells (Orlando et al, 2004). Indeed, sst2 is considered a good prognosis factor due to its association with low proliferative and invasive breast cancers (Orlando et al, 2004). Moreover, sst2 expression loss in certain cancer cells results in the elimination of an autocrine inhibitory feedback loop, which leads to phenotypic and functional alterations (Benali et al, 2000;Leu et al, 2008), including epithelial-to-mesenchymal transition, and increased cell proliferation (Leu et al, 2008) and metastasis (Benali et al, 2000).…”

Prognostic value of somatostatin receptor subtype 2 expression in colorectal cancer

“…Indeed, these findings are in contrast not only with the aforementioned data in neuroblastoma, but also with results we recently obtained in a prospective study on a large group of patients affected by breast cancer [21]. In the latter we found an upregulation of sst2 mRNA expression in those breast tumors that on the basis of conventional predictive parameters are expected to have a better prognosis.…”

Identification of transcriptional regulatory elements in the human somatostatin receptor sst2 promoter and regions including estrogen response element half-site for estrogen activation

“…Similar effects of estrogen on sst2 mRNA expression and sst2 binding activity were reported for human breast cancer cell lines (Xu et al 1996). Importance of the estrogen-induced sst2 expression is recognized in the recent oncological studies, in which, for example, the effectiveness of endocrine therapy can be assessed with a whole-body imaging of 99m Tc-labeled depreotide that binds to sst2 since its expression associates with functional estrogen receptor (ER) positivity and may lead to a better clinical prognosis (Van Den Bossche et al 2004, 2006, Orlando et al 2004, Murdie 2006. Nevertheless, the mechanism of transcriptional regulation by estrogen has been poorly understood in the human sst2 gene.…”