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Selective estrogen receptor modulators decrease invasiveness in pituitary adenoma cell lines AtT-20 and TtT/GF by
Zhuo Zhang1,2, Jörg W Bartsch1, Julia Benzel1,3
1Department of Neurosurgery, University Hospital Marburg, Germany.
FEBS Open Bio
|October 8, 2020
Summary
Selective estrogen receptor modulators (SERMs) reduce pituitary adenoma cell invasiveness. These compounds downregulate key proteases, matrix metalloproteinase-14 (MMP-14) and A disintegrin and metalloproteinase-12 (ADAM12), inhibiting tumor spread.
Area of Science:
- Endocrinology and Molecular Biology
- Cancer Research
Background:
- Pituitary adenomas (PAs) are common tumors affecting hormone regulation.
- Selective estrogen receptor modulators (SERMs) are known to influence PA cell behavior.
Purpose of the Study:
- To investigate the effects of clinically relevant SERMs on PA cell invasiveness.
- To analyze the impact of SERMs on the expression of invasion-related proteases, specifically MMP-14 and ADAM12.
Main Methods:
- Murine PA cell lines (AtT-20 and TtT/GF) were treated with three SERMs: bazedoxifene, clomiphene, and raloxifene.
- Gene and protein expression of MMP-14 and ADAM12 were assessed.
- Gene silencing techniques were employed to confirm the role of MMP-14 and ADAM12 in cell invasion.
Main Results:
- All tested SERMs significantly reduced the invasiveness of both PA cell lines.
- SERMs decreased ADAM12 mRNA expression in both cell lines and MMP-14 mRNA in TtT/GF cells.
- Gene silencing of ADAM12 and MMP-14 confirmed their role in PA cell invasion, with silencing leading to decreased invasion rates.
Conclusions:
- SERMs effectively attenuate the invasiveness of murine pituitary adenoma cells.
- This anti-invasive effect is mediated through the downregulation of invasion-related proteases, MMP-14 and ADAM12.

