[Study on the modulation of estrogen receptor isoforms alpha in endometrial carcinoma cells using antisense oligodeoxyribonucleotides].
OBJECTIVE
To verify the roles of estrogen receptor alpha in the tumogenesis of endometrial cancer in relationship with estrogen and tamoxifen, and to explore an efficient way to modulate the expression of estrogen receptor (ER) isoform alpha to built up a model of endometrial cancer cells expressing predominant one isoform of ERs for ultimately probing therapeutical and preventive antiestrogen for endometrial cancer.


METHODS
A series of oligodeoxyribonucleotides against regions of the human ERalpha was synthesized and tested in human endometrial cancer cell line (HEC-1B cells) that expressed functional ERalpha. The expressions of ER isoforms were detected by Western blot using specific antibody. The change of HEC-1B cell proliferation in response to 17beta-estradiol(E2) and tamoxifen(TAM) under the impact of antisense oligodeoxyribonucleotides (AS-ODN) was studied.


RESULTS
(1) Transfection with AS-ODN directed against the human ERalpha significantly inhibited ERalpha protein expression. (2) The proliferation of endometrial cancer cell line HEC-1B could be increased by both E(2) and TAM. The cells lost the ability to proliferate in response to E(2) after being transfected with ERalpha-AS-ODN at hours 24, 48 and 72. After being transfected with ERalpha-AS-ODN, HEC-1B cells lost the ability to proliferate in response to TAM at hour 48.


CONCLUSIONS
(1) AS-ODNs directed against the human ERalpha can inhibit the expression of ER alpha effectively. The method can be used to built up a model of endometrial cancer cells expressing predominant one isoform of ERs. (2) ERalpha may be the primary receptor in the proliferation of HEC-1B cells in response to 17beta-estradiol and tamoxifen.
Zhang
Yan
Y
Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing 100034, China.
Liao
Qin-ping
QP
Yu
Li
L
Chen
Chun-ling
CL
Zhao
Jian
J
D049109:Cell Proliferation / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D006801:Humans; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics* / Q000494:pharmacology; D020033:Protein Isoforms / Q000096:biosynthesis; D013629:Tamoxifen / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
D047628:Estrogen Receptor alpha; D020319:Oligodeoxyribonucleotides, Antisense; D020033:Protein Isoforms; D013629:Tamoxifen; D004958:Estradiol