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Oestrogen-mediated regulation of somatostatin receptor expression in human breast cancer cell lines assessed with 99mTc-depreotide

  • Molecular Imaging
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Investigating three somatostatin receptor (SSTR)-positive (+) human breast cancer cell lines, Xu et al. found a time- and dose-dependent up- or down-regulation of SSTR2 mRNA expression by 17β-oestradiol (E2) or the anti-oestrogen tamoxifen, respectively, in the two oestrogen receptor-positive (ER+) cell lines but not in the oestrogen receptor-negative (ER−) cell line. This study aimed to confirm the findings of Xu et al. at the protein level by means of western blotting and saturation binding studies using 99mTc-depreotide (NeoSpect). The ER+/SSTR+ ZR75-1 and T47D and SSTR+/ER− MDA MB231 breast cancer cell lines were exposed to 1 nM E2 or a combination of 1 nM E2 plus 100 nM tamoxifen or ICI 182 780 (Faslodex) for 48 h. Exposed and non-exposed controls were incubated with increasing concentrations of 99mTc-depreotide (0.5 nM–15 nM) in the absence and the presence of 20 μM of octreotide. Scatchard-Rosenthal plots were derived using commercially available software. SSTR subtypes responsible for E2-induced changes in 99mTc-depreotide binding were identified by means of western blotting. Mean K d values for 99mTc-depreotide were 13 nM, 7 nM and 4 nM for T47D, ZR75-1 and MDA MB231 cells, respectively. After stimulation with E2, the ER+ cell line T47D demonstrated a mean increase of 81% (P<0.05) in 99mTc-depreotide binding. Adding the partial agonist tamoxifen and full antagonist ICI 182 780 to E2 blocked the induced increase in T47D cells, either reducing SSTR expression or restoring it to control levels. ZR75-1 cells stimulated with E2 showed a mean decrease in 99mTc-depreotide binding of 36% as compared to control cells; this difference, however, proved to be not statistically significant. Similarly, B max values did not change in ZR75-1 cells exposed to E2 in combination with an ER antagonist as compared to control cells. Finally, no influence of E2 on 99mTc-depreotide binding was observed in the ER− cell line MDA MB231. Both SSTR2 and SSTR5 were expressed at high levels in T47D cells and ZR75-1 cells. SSTR5 drastically increased in the absence of E2 and was restored to the original detection level after E2 treatment. The presented findings support an oestrogen-dependent regulation of SSTR expression in breast cancer cell lines.

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Acknowledgements

The authors wish to thank Dr. C.E. Stidsen (Novo Nordisk, Denmark) for providing the SSTR subtype-specific antibodies and Prof. M. Mareel for offering encouraging support during the binding experiments. Dr. B. Van Den Bossche has prepared this manuscript as part of her PhD course in the Nuclear Medicine Unit at the University of Rome “La Sapienza” and wishes to thank Prof. F. Scopinaro and Dr. A. Signore for their support and useful suggestions in preparing the manuscript.

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Authors and Affiliations

  1. Division of Nuclear Medicine, Ghent University Hospital, De Pintelaan 185, 9000B, Ghent, Belgium

    B. Van Den Bossche, E. D’haeninck, F. De Vos, R. A. Dierckx & C. Van de Wiele

  2. Laboratory of Experimental Cancerology, Ghent University Hospital, Ghent, Belgium

    M. Bracke

  3. Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium

    S. Van Belle

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  1. B. Van Den Bossche
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  2. E. D’haeninck
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  3. F. De Vos
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  4. R. A. Dierckx
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Correspondence to B. Van Den Bossche.

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Van Den Bossche, B., D’haeninck, E., De Vos, F. et al. Oestrogen-mediated regulation of somatostatin receptor expression in human breast cancer cell lines assessed with 99mTc-depreotide. Eur J Nucl Med Mol Imaging 31, 1022–1030 (2004). https://doi.org/10.1007/s00259-004-1500-6

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  • DOI: https://doi.org/10.1007/s00259-004-1500-6

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