title: Non-nuclear activation of signal transducer and activator of transcription 3 by 17β- estradiol in endometrial cancer cells.
abstract: Why estrogen hyperstimulation can lead to endometrial carcinogenesis has not been fully clear yet. Non-nuclear action of estrogen has arised much attention of many experts. Signal transducer and activator of transcription 3 is a very important signal molecule, which plays vital role in endometrial canver. The present study is oriented to the problem whether estrogen can activate STAT3 by non-nuclear action in endometrial cancer cells. So, the levels of phosphorylated STAT3 (P-STAT3) and total STAT3 were examined by western blot in endometrial cancer cells including Ishikawa with rich-expressed estrogen receptor (ER) and HEC-1A with poor-expressed ER after stimulation with 1μM estradiol (E2) at different time points and at varied doses of E2 for optimal time. Inhibitory role of AG490 on activation of STAT3 induced by E2 was also tested. P-STAT3/STAT3 was used as a measure of activation of STAT3. We found that maximum P-STAT3/STAT3 took place at 15 min in both Ishikawa cells and HEC-1A cells. The activation of STAT3 elicited gradually with increasing doses of E2. AG490 stopped the activating STAT3 in the same dose-dependent manner in both endometrial cancer cells. The results demonstrate that E2 is able to activate STAT3 in both Ishikawa with rich-expressed ER and HEC-1A with poor-expressed ER endometrial cancer cells by non-nuclear action, which provides the preliminary laboratory basis for the probability of endometrial adenocarcinoma treatment with blockage of STAT3 signaling, especially for ER-poor endometrial adenocarcinoma.
authors: department of Obstetrics and Gynecology, The First Affiliated Hospital, Zheng Zhou University, China. grx0322@yahoo.com.cn
authors: R X
authors: RX
authors: Guo
authors: R F
authors: RF
authors: Zhang
authors: X Y
authors: XY
authors: Wang
authors: L X
authors: LX
authors: Li
authors: H R
authors: HR
authors: Shi
authors: Y H
authors: YH
authors: Qiao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D011960:Receptors, Estrogen / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004967:Estrogens; D011960:Receptors, Estrogen; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D004958:Estradiol