Effects of fulvestrant, an estrogen receptor antagonist, on MMQ cells and its mechanism.
OBJECTIVE
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.


METHODS
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.
Li
Chuzhong
C
Capital Medical University, Beijing, China.
Sun
Zelin
Z
Gui
Songbai
S
Liu
Fangjun
F
Zhang
Yazhuo
Y
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D000077267:Fulvestrant; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D015175:Prolactinoma / Q000188:drug therapy* / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol; D011388:Prolactin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4