OBJECTIVES: Unlike the successful endocrine therapy of breast cancers and other estrogen-dependent diseases, little is known about the effect of anti-estrogen treatment on pituitary tumors. Our objectives were to study the effect of fulvestrant, a new type anti-estrogen devoid of any agonistic activities, on prolactinoma cell line MMQ in vitro and its possible mechanisms. DESIGN: In the experiment, the prolactin concentration, proliferation and apoptosis of the MMQ cell were measured to investigate the anti-tumor effect of the fulvestrant. The expression of estrogen receptor (ESR) mRNA and protein and MAPK pathway-related proteins ERK1 and 2, JNK, and p38 were measured to investigate the possible mechanisms. RESULTS: Fulvestrant significantly inhibited prolactin secretion (up to 85.5%), decreased proliferation (IC50 = 32.4 nmol/l), and promoted apoptosis of the MMQ cells. CONCLUSIONS: The suppression was possibly mediated by inhibition of ESR mRNA expression, down-regulation of ESR expression and activation of MAPK pathway-related proteins. Thus, fulvestrant has suppressive effects on prolactinoma cells and its anti-tumor mechanism appears to be related to the inhibition of ESR and the MAPK pathway.
OBJECTIVES: Unlike the successful endocrine therapy of breast cancers and other estrogen-dependent diseases, little is known about the effect of anti-estrogen treatment on pituitary tumors. Our objectives were to study the effect of fulvestrant, a new type anti-estrogen devoid of any agonistic activities, on prolactinoma cell line MMQ in vitro and its possible mechanisms. DESIGN: In the experiment, the prolactin concentration, proliferation and apoptosis of the MMQ cell were measured to investigate the anti-tumor effect of the fulvestrant. The expression of estrogen receptor (ESR) mRNA and protein and MAPK pathway-related proteins ERK1 and 2, JNK, and p38 were measured to investigate the possible mechanisms. RESULTS:Fulvestrant significantly inhibited prolactin secretion (up to 85.5%), decreased proliferation (IC50 = 32.4 nmol/l), and promoted apoptosis of the MMQ cells. CONCLUSIONS: The suppression was possibly mediated by inhibition of ESR mRNA expression, down-regulation of ESR expression and activation of MAPK pathway-related proteins. Thus, fulvestrant has suppressive effects on prolactinoma cells and its anti-tumor mechanism appears to be related to the inhibition of ESR and the MAPK pathway.