J Gastric Cancer.  2013 Sep;13(3):172-178.

Effects of 17beta-Estradiol and Estrogen Receptor Antagonists on the Proliferation of Gastric Cancer Cell Lines

• Kim MJ
• Cho SI
• Lee KO
• Han HJ
• Song TJ
• Park SH

Abstract

PURPOSE
The aims of this study were as follow: 1) to de scribe the expression status of estrogen receptor-alpha and -beta mRNAs in five gastric carcinoma cell lines; 2) to evaluate in vitro the effects of 17beta-estradiol and estrogen receptor antagonists on the proliferation of the cell lines.
MATERIALS AND METHODS
Detection of estrogen receptor-alpha and estrogen receptor-beta mRNA in five human gastric cancer cell lines (AGS, KATO III, MKN28, MKN45 and MKN74) was made by the reverse transcription-polymerase chain reaction system. To evaluate the effect of 17beta-estradiol and estrogen receptor antagonists on the proliferation of gastric cancer cell line, the cell lines which expressed both es trogen receptors were chosen and treated with 17beta-estradiol and estrogen receptor antagonists (methyl-piperidino-pyrazole and pyrazolo [1,5-a] pyrimidine). Cell proliferation was assessed with the methylthiazol tetrazolium test.
RESULTS
Estrogen receptor-alpha and estrogen receptor-beta mRNAs were expressed in three (KATO III, MKN28 and MKN45) and all of the five gastric cancer cell lines, respectively. At higher concentrations, 17beta-estradiol inhibited cell growth of MKN28, MKN45 and KATO III cell lines. Neither estrogen receptor-alpha nor estrogen receptor-beta antagonist blocked the anti-proliferative effect of 17beta-estradiol.
CONCLUSIONS
Our results indicate that estrogen receptor-beta mRNAs are preferentially expressed in gastric cancers and also imply that hormone therapy rather than estrogen receptor blockers may be a useful strategy for the treatment of estrogen receptor-beta positive gastric cancer. Its therapeutic significance in gastric cancer are, however, limited until more evidence of the roles of estrogen receptors in the gastric cancer are accumulated.

Keyword

Estrogens; Receptors, estrogen; Stomach neoplasms; Cell line

MeSH Terms

Cell Line
Cell Proliferation
Estrogens
Humans
Receptors, Estrogen
RNA, Messenger
Stomach Neoplasms
Estrogens
RNA, Messenger
Receptors, Estrogen

Figure

• 

  Fig. 1 Reverse transcription-polymerase chain reaction of estrogen receptor (ER)-α (A) and ER-β (B) mRNAs in five human gastric cancer cell lines (AGS, KATO III, MKN28, MKN45 and MKN74). MCF7 cells were used for controls for positive ERs. ER-α mRNA was detected in the KATO III, MKN28 and MKN45. ER-α/β-actin ratio of KATO III, MKN28 and MKN45 were 6.17, 0.86 and 0.04, respectively. In contrast, ER-β mRNA was detected in all the five cell lines. ER-α/β-actin ratio of AGS, KATO III, MKN28, MKN45 and MKN74 were 1.33, 1.74, 0.76, 2.06 and 1.93, respectively.

• 

  Fig. 2 Effect of 17β-estradiol on the proliferation of three gastric cancer cell lines (MKN28, 45 and KATO III). The plots represent the effects of increasing 17β-estradiol concentrations on the conversion of methylthiazol tetrazolium to formazan. All results represent the means and the 25th & 75th percentiles of three different experiments. *P<0.05 compared with control (Wilcoxon rank sum test).

• 

  Fig. 3 Effect of estrogen receptor (ER)-α and -β antagonists on the viability of 17β-estradiol-treated KATO III cell line. Neither ER-α nor ER-β antagonist blocked anti-proliferative effect of 17β-estradiol. 17b = 17β-estradiol; M = methyl-piperidino-pyrazole (MPP, ER-α antagonist); P = pyrazolo [1,5-a] pyrimidine (PHTPP, ER-β antagonist).

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