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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.
Abstract:
Selective estrogen receptor modulators (SERMs) significantly affect survival and invasiveness of rodent pituitary adenoma (PA) cells. The impact of three clinically relevant SERMs (bazedoxifene, clomiphene, raloxifene) on invasiveness and on gene and protein expression of invasion-related proteases [matrix metalloproteinase-14 (MMP-14) and A disintegrin and metalloproteinase-12 (ADAM12)] was analyzed in murine PA cells (AtT-20 and TtT/GF). All SERMs significantly decreased cell invasiveness. Moreover, SERMs significantly decreased expression of ADAM12 mRNA in both cell lines and of MMP-14 mRNA in TtT/GF cells. Invasion rates of AtT-20 and TtT/GF significantly decreased after ADAM12 gene silencing, and the invasion rate of TtT/GF cells significantly decreased after MMP-14 gene silencing. All SERMs affected ADAM12 protein expression in AtT-20 cells whereas bazedoxifene and raloxifene decreased MMP-14 protein expression in TtT/GF cells. We conclude that SERMs attenuate invasiveness of murine PA cells by downregulating expression levels of invasion-related proteases MMP-14 and ADAM12.
Insights
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.
