[Modulation and function of estrogen receptor isoforms alpha and beta in endometrial carcinoma cells].

Abstract

OBJECTIVE:

To explore an efficient way to modulate the expression of estrogen receptor (ER) alpha and beta, and to build up a model of endometrial cancer cell expressing predominantly one isoform of ER and to verify the roles of ER alpha and beta in the tumorigenesis of endometrial cancer associated with estrogen and tamoxifen (TAM).

METHODS:

A series of oligodeoxyribonucleotides (ODN) against alpha or beta regions of ER alpha or beta were synthesized and tested in human endometrial cancer cell lines (Ishikawa) that express functional ER alpha and beta. The expressions of two ER isoforms were detected by western blot using specific antibodies. Then we studied the change of Ishikawa proliferation in response to 17beta-estradiol and TAM under the influence of antisense ODN.

RESULTS:

(1) Transfection with antisense ODN directed against the ERalpha and ERbeta could significantly inhibit target protein production. (2) 17beta-estradiol could increase the proliferation of Ishikawa cells, but they lost the ability to proliferate in response to 17beta-estradiol after transfected with ERalpha antisense ODN especially at hours 24, 48 and 72 (P < 0.05). There was no obvious change in cell numbers of Ishikawa in response to 17beta-estradiol which were transfected with ERbeta antisense ODN. (3) TAM could also increase the growth of Ishikawa cells. After transfected with ERalpha antisense ODN, the cells lost the ability to proliferate in response to TAM at hours 24, 48 and 72 (P < 0.05). The inhibition was also seen in Ishikawa cells transfected with ERbeta antisense ODN at hour 72.

CONCLUSIONS:

(1) Antisense ODN directed against the ERalpha or ERbeta can inhibit the expression of ERalpha or ERbeta effectively. (2) ERalpha may be the primary receptor in the proliferation of Ishikawa cells in response to 17beta-estradiol. Both ERalpha and ERbeta are involved in agonist impact of TAM on endometrial cancer cells.

• Authors: Yan Zhang, Qin-ping Liao, Li Yu, Jian Zhao, Chun-ling Chen
• Journal: Zhonghua fu chan ke za zhi (Zhonghua Fu Chan Ke Za Zhi) Vol. 40 Issue 8 Pg. 558-61 (Aug 2005) ISSN: 0529-567X [Print] China
• PMID: 16202298 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Estrogen Receptor alpha
• Estrogen Receptor beta
• Estrogens
• Oligodeoxyribonucleotides, Antisense
• Tamoxifen

Topics

• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Endometrial Neoplasms (genetics, metabolism)
• Estrogen Receptor alpha (physiology)
• Estrogen Receptor beta (physiology)
• Estrogens (pharmacology)
• Female
• Humans
• Oligodeoxyribonucleotides, Antisense (pharmacology)
• Tamoxifen (pharmacology)
• Transfection (methods)