TY - JOUR
T1 - A stable human progesterone receptor expressing HeLa reporter cell line as a tool in chemical evaluation at the different cell-cycle phases
AU - Mori, Tetsushi
AU - Murata, Mai
AU - Yoshino, Tomoko
AU - Nakasono, Satoshi
AU - Saito, Fumiyo
AU - Takeyama, Haruko
AU - Matsunaga, Tadashi
N1 - Funding Information:
This work was supported by Grant-in-Aid for Scientific Research on Priority Areas “Lifesurveyor” (17066002) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
PY - 2009/4/25
Y1 - 2009/4/25
N2 - Specific molecular events, characteristic of each cell-cycle phase may have direct effect to the functionality of nuclear receptors. Based on this understanding, the evaluation of lipophilic chemicals at the different cell-cycle phases is significant and should be considered. In order to achieve the aim of performing large-scale dose-response analysis on the effects of lipophilic chemicals at the different cell-cycle phases, a stable, sensitive and highly selective human progesterone receptor (hPR) expressing HeLa reporter cell line, hPRLuc-20, was established. Upon the establishment of the hPRLuc-20 cells, they were synchronized to the G1, S and G2 phases and treated with progesterone (PROG) and promegestone (R5020). The cells successfully showed that at the different cell-cycle phase, both agonists resulted in different cellular responses. The differences in response supports that hPR expressed within the hPRLuc-20 cells do respond in a cell-cycle dependent manner, thus showing the cells' compatibility in large-scale dose-response analyses of chemicals. It is hopeful that the advanced application of the hPRLuc-20 cells could contribute to provide fundamental hints to further understand the function of hPR, and provide key observations to elucidate the nature of these chemicals with hPR, its corresponding co-regulators and transcription factors.
AB - Specific molecular events, characteristic of each cell-cycle phase may have direct effect to the functionality of nuclear receptors. Based on this understanding, the evaluation of lipophilic chemicals at the different cell-cycle phases is significant and should be considered. In order to achieve the aim of performing large-scale dose-response analysis on the effects of lipophilic chemicals at the different cell-cycle phases, a stable, sensitive and highly selective human progesterone receptor (hPR) expressing HeLa reporter cell line, hPRLuc-20, was established. Upon the establishment of the hPRLuc-20 cells, they were synchronized to the G1, S and G2 phases and treated with progesterone (PROG) and promegestone (R5020). The cells successfully showed that at the different cell-cycle phase, both agonists resulted in different cellular responses. The differences in response supports that hPR expressed within the hPRLuc-20 cells do respond in a cell-cycle dependent manner, thus showing the cells' compatibility in large-scale dose-response analyses of chemicals. It is hopeful that the advanced application of the hPRLuc-20 cells could contribute to provide fundamental hints to further understand the function of hPR, and provide key observations to elucidate the nature of these chemicals with hPR, its corresponding co-regulators and transcription factors.
KW - Cell cycle
KW - Human progesterone receptor
KW - Lipophilic chemicals
KW - Stable cell reporter gene assay
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U2 - 10.1016/j.toxlet.2009.01.016
DO - 10.1016/j.toxlet.2009.01.016
M3 - Article
C2 - 19429233
AN - SCOPUS:61349202102
SN - 0378-4274
VL - 186
SP - 123
EP - 129
JO - Toxicology Letters
JF - Toxicology Letters
IS - 2
ER -