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Dominant Negative ER Induces Apoptosis in GH4 Pituitary Lactotrope Cells and Inhibits Tumor Growth in Nude Mice

Title
Dominant Negative ER Induces Apoptosis in GH4 Pituitary Lactotrope Cells and Inhibits Tumor Growth in Nude Mice
Authors
Eun Jig Lee;W. Rachel Duan;J. Larry Jameson;Barry D. Gehm;Monika Jakacka
Issue Date
2001
Journal Title
Endocrinology
ISSN
0013-7227
Citation
Endocrinology, Vol.142(9) : 3756~3763, 2001
Abstract
The ER plays an important role in the proliferation and differentiation of lactotrope tumor cells. GH4 cells were infected with adenoviral vectors (AdL540Q and Ad1–536) to investigate the ability of dominant negative ER mutants to affect the regulation of gene expression and cell growth by endogenous ER. The dominant negative mutants suppressed estradiol stimulation of an estrogen-responsive reporter gene and the PRL promoter in these cells. AdL540Q or Ad1–536 infection also inhibited GH4 cell growth and induced apoptosis, increasing the expression of the proapoptotic Bax protein and decreasing the expression of antiapoptotic Bcl-2. AdwtER-infected cells also showed decreased Bcl-2 protein. E2-induced activation of p38 MAPK, an enzyme that may participate in apoptosis, was observed in cells infected with AdwtER, AdL540Q, and Ad1–536. Consistent with the apoptotic effects in vitro, infection of GH4 cells with AdL540Q or Ad1–536 inhibited the ability of the cells to form tumors in nude mice. These results indicate that dominant negative ER mutants induce apoptosis of GH4 cells and suppress tumor formation and development. The delivery of dominant negative ERs by adenoviral vectors may provide an alternative modality for the targeted therapy of pituitary lactotrope adenomas and other estrogen-responsive tumors.
URI
http://press.endocrine.org/doi/abs/10.1210/endo.142.9.8372

http://ir.ymlib.yonsei.ac.kr/handle/22282913/142458
DOI
10.1210/endo.142.9.8372
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
Yonsei Authors
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