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Estrogen regulates somatostatin receptor subtype 2 messenger ribonucleic acid expression in human breast cancer cells
1Department of Medicine, State University of New York at Stony Brook, 11794, USA.
Abstract:
Somatostatin (SRIF) and its analogs exhibit antiproliferative effects that are mediated by SRIF receptors (sst) present in responsive normal and neoplastic tissue including breast cancer. However, information regarding regulation of sst gene expression in cancer cells and modulation of SRIF binding is limited. In the present study we have determined the pattern of sst subtype messenger RNA (mRNA) expression in human breast cancer cells. Furthermore, we investigated the effect of 17beta-Estradiol (E2) treatment on steady state levels of sst mRNA by solution hybridization/nuclease protection analysis and on SRIF binding to membranes of treated cells by receptor binding assay. sst2 mRNA was highly expressed in T47D, ZR75-1, and MDA MB231 cells. Transcripts for sst1 were also detected at very low levels in ZR75-1 cells, whereas sst5 mRNA was expressed at low levels in MCF-7 cells. No sst subtype was detected in MDA MB 435s cells. When the estrogen receptor (ER)(+) cell lines T47D and ZR75-1 were cultured in phenol red-free media plus CS-FCS, sst2 mRNA levels decreased by 60-80% compared with complete serum controls. Adding E2 restored sst2 mRNA levels to control in both cell lines. Moreover, the effect of E2 on sst2 gene expression in T47D and ZR75-1 cells was dose- and time-dependent. In contrast, neither culturing in phenol red-free media plus CS-FCS nor E2 influenced sst2 expression in the ER(-) cell line MDA MB231. E2-induced regulation of SRIF binding and sst2 mRNA expression occurred in a parallel manner in T47D cells but were dissociated in ZR75-1 cells. The pure antiestrogen ICI 182 780 inhibited E2-induced sst2 expression in both cell lines. The antiestrogen 4OH tamoxifen showed strong estrogen-like effects on sst2 mRNA expression in T47D cells, while acting as a potent antiestrogen in ZR75-1 cells. Thus, these data suggest that E2 regulates sst2 expression in human breast cancer cell lines through the ER. The human breast cancer cell lines provide a useful model to examine the molecular mechanisms involved in E2 regulation of sst2 expression.
Insights
17beta-Estradiol (E2) regulates somatostatin receptor subtype 2 (sst2) gene expression in human breast cancer cells via the estrogen receptor (ER). This study explores E2
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Somatostatin analogs have antiproliferative effects on cancer cells.
- Regulation of somatostatin receptor (sst) gene expression and somatostatin binding in cancer is not well understood.
- Estrogen's role in breast cancer progression is significant.
Purpose of the Study:
- To determine somatostatin receptor subtype messenger RNA (mRNA) expression patterns in human breast cancer cells.
- To investigate the effect of 17beta-Estradiol (E2) on sst mRNA levels and somatostatin binding.
- To elucidate the role of the estrogen receptor (ER) in mediating these effects.
Main Methods:
- Solution hybridization/nuclease protection assay to quantify sst mRNA levels.
- Receptor binding assay to measure somatostatin binding to cell membranes.
- Culture of estrogen receptor-positive and -negative breast cancer cell lines with and without E2 and antiestrogens.
Main Results:
- sst2 mRNA was highly expressed in ER-positive (T47D, ZR75-1) and ER-negative (MDA MB231) breast cancer cells.
- E2 treatment restored E2-depleted sst2 mRNA levels in ER-positive cells in a dose- and time-dependent manner.
- Antiestrogens ICI 182 780 and 4OH tamoxifen modulated E2-induced sst2 expression, indicating ER-mediated regulation.
Conclusions:
- 17beta-Estradiol (E2) significantly regulates sst2 gene expression in human breast cancer cell lines through the estrogen receptor (ER).
- Breast cancer cell lines serve as a valuable model for studying E2 regulation of sst2 expression.
- Findings suggest potential therapeutic strategies targeting the somatostatin receptor pathway in breast cancer.