Modulation of ATP-induced calcium signaling by progesterone in T47D-Y breast cancer cells.
Extracellular ATP activates purinergic (P(2)) receptors with an increase in intracellular calcium and phosphorylation of MAPK. In this study we have investigated the effect of progesterone/progestin on ATP-induced calcium mobilization and phosphorylation of the kinase ERK in the T47D-Y breast cancer cell line that exhibits no detectable nuclear progesterone receptor expression. Brief pretreatment with progesterone/progestin results in a dose dependent inhibition of ATP-induced intracellular calcium mobilization, and inhibition of ERK phosphorylation. Response to a cell impermeable ligand and inhibition of the response by an inactivating antibody suggests a mechanism of action at the plasma membrane. These results in T47D-Y cells strongly suggest that progesterone can act in a rapid non-nuclear manner to inhibit extracellular ATP effects on intracellular calcium mobilization and ERK activation. This research provides an example of progesterone action in a breast cancer cell line lacking expression of the classical nuclear progesterone receptors.
Lee
Karen L
KL
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Duke University, Durham, NC 27710, USA.
Dai
Qunsheng
Q
Hansen
Elizabeth L
EL
Saner
Carrie N
CN
Price
Thomas M
TM
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002458:Cell Fractionation; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation; D011374:Progesterone / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism
D011372:Progestins; D011980:Receptors, Progesterone; D018048:Receptors, Purinergic P2; D011374:Progesterone; D000255:Adenosine Triphosphate; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium