A stable human progesterone receptor expressing HeLa reporter cell line as a tool in chemical evaluation at the different cell-cycle phases.
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 G(1), S and G(2) 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.
Department of Biotechnology, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan.
Tetsushi
T
Mori
Mai
M
Murata
Tomoko
T
Yoshino
Satoshi
S
Nakasono
Fumiyo
F
Saito
Haruko
H
Takeyama
Tadashi
T
Matsunaga
D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D017930:Genes, Reporter / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008156:Luciferases / Q000096:biosynthesis; D011374:Progesterone / Q000494:pharmacology; D011372:Progestins / Q000494:pharmacology; D011397:Promegestone / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000378:metabolism*; D012995:Solubility
D008055:Lipids; D011372:Progestins; D011980:Receptors, Progesterone; D011374:Progesterone; D011397:Promegestone; D008156:Luciferases