TY - JOUR
T1 - Cytonuclear estrogen receptor alpha regulates proliferation and migration of endometrial carcinoma cells
AU - Saimi, Mierxiati
AU - Moriya, Shota
AU - Li, Zhong Lian
AU - Miyaso, Hidenobu
AU - Nagahori, Kenta
AU - Kawata, Shinichi
AU - Omotehara, Takuya
AU - Ogawa, Yuki
AU - Hino, Hirotsugu
AU - Miyazawa, Keisuke
AU - Sakabe, Kou
AU - Itoh, Masahiro
N1 - Publisher Copyright:
© 2021, Tokai University School of Medicine. All rights reserved.
PY - 2021
Y1 - 2021
N2 - Objective: The effects of estrogen on cells are mediated by the estrogen receptor α (ERα) which localizes at the peri-membrane, cytoplasm, and the nucleus of cells. Therefore, we intended to investigate how cytonuclear ERα plays its roles in different cellular activities. Methods: We used amino acid substituted ERα that localized at the cytoplasm and nucleus but has no direct DNA-binding activities. ERα-negative endometrial carcinoma cells (ERα-) were stably transfected with plasmid of human ERα carrying a substituted phenylalanine at position 445 with alanine (ERα-F445A). Treated with 17β-estrogen (E2) or bazedoxifene (BDF), cell proliferation, migration, and expression of kinases related to ERα signal transduction pathways were observed. Results: E2 (40 nM) significantly activated proliferation in ERα-F445A cells, but not in ERα-cells. Similarly, E2 significantly activated cell migration in ERα-F445A cells, rather than that in ERα-cells. While no obvious change in the amount of the non-phosphorylated mammalian target of Rapamycin (mTOR), the expression of mTOR phosphorylated at serine 2448 decreased, which was recovered in presence of 17β-estrogen (E2) in the ERα-F445A cells. On the other hand, the expression of focal adhesion kinase (FAK) phosphorylated at tyrosine at 297 was attenuated in the ERα-F445A cells treated with E2. Conclusion: It is suggested that the cytonuclear ERα-F445A induces phosphorylation of kinases in downstream pathways, which regulate cell proliferation and migration.
AB - Objective: The effects of estrogen on cells are mediated by the estrogen receptor α (ERα) which localizes at the peri-membrane, cytoplasm, and the nucleus of cells. Therefore, we intended to investigate how cytonuclear ERα plays its roles in different cellular activities. Methods: We used amino acid substituted ERα that localized at the cytoplasm and nucleus but has no direct DNA-binding activities. ERα-negative endometrial carcinoma cells (ERα-) were stably transfected with plasmid of human ERα carrying a substituted phenylalanine at position 445 with alanine (ERα-F445A). Treated with 17β-estrogen (E2) or bazedoxifene (BDF), cell proliferation, migration, and expression of kinases related to ERα signal transduction pathways were observed. Results: E2 (40 nM) significantly activated proliferation in ERα-F445A cells, but not in ERα-cells. Similarly, E2 significantly activated cell migration in ERα-F445A cells, rather than that in ERα-cells. While no obvious change in the amount of the non-phosphorylated mammalian target of Rapamycin (mTOR), the expression of mTOR phosphorylated at serine 2448 decreased, which was recovered in presence of 17β-estrogen (E2) in the ERα-F445A cells. On the other hand, the expression of focal adhesion kinase (FAK) phosphorylated at tyrosine at 297 was attenuated in the ERα-F445A cells treated with E2. Conclusion: It is suggested that the cytonuclear ERα-F445A induces phosphorylation of kinases in downstream pathways, which regulate cell proliferation and migration.
KW - Endometrium
KW - Estrogen receptor alpha
KW - Focal adhesion kinase (FAK)
KW - Mammalian target of Rapamycin (mTOR)
KW - Migration
UR - http://www.scopus.com/inward/record.url?scp=85104169600&partnerID=8YFLogxK
M3 - Article
C2 - 33835469
AN - SCOPUS:85104169600
SN - 0385-0005
VL - 46
SP - 7
EP - 16
JO - Tokai Journal of Experimental and Clinical Medicine
JF - Tokai Journal of Experimental and Clinical Medicine
IS - 1
ER -