title: 17 beta-estradiol-induced increases in glucose-regulated protein 78kD and 94kD protect human breast cancer T47-D cells from thermal injury.
abstract: Heat shock alters the susceptibility of tumor cells to chemotherapeutic agents. We conducted experiments to study the regulation of expression of heat shock proteins (HSP) in 17 beta-estradiol-treated T47-D cells, a human breast cancer cell line. Cells exposed to 17 beta-estradiol for 24-48 h displayed increased expression of glucose regulated protein 78kD (GRP-78) and 94kD (GRP-94), as shown by [35S]methionine incorporation and Western blotting experiments. The increase was time (5 h to 48 h)-dependent at 1 nM and 1 microM 17 beta-estradiol. Cells overexpressing GRP-78 and -94 after treatment with 17 beta-estradiol displayed resistance against heat shock (47 degrees C for 50 min)-induced death. Removal of external Ca2+ or treatment of cells with BAPTA (a Ca2+ chelator) did not alter the synthesis of GRP-78 and -94, suggesting that the 17 beta-estradiol effect on the synthesis of GRP-78 and -94 is Ca(2+)-independent. In addition, exposure of cells to 17 beta-estradiol up to 100 microM did not increase [Ca2+]i, which further supports the view that the estrogen-induced GRPs are not regulated by [Ca2+]i. Treatment with H89 (a protein kinase A inhibitor, 1 microM, 30 min) or GF-109203X (a protein kinase C inhibitor, 1 microM, 30 min) also did not change the GRP synthesis, indicating that protein kinase A and C are not involved in regulation of GRP synthesis.
authors.affiliation: Department of Clinical Physiology, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA. Dr._Juliann_Kiang@WRSMTP-ccmail.army.mil
authors.forename: J G
authors.initials: JG
authors.lastname: Kiang
authors.forename: I D
authors.initials: ID
authors.lastname: Gist
authors.forename: G C
authors.initials: GC
authors.lastname: Tsokos
mesh_terms: D002118:Calcium / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006358:Hot Temperature; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; C018551:glucose-regulated proteins; D004958:Estradiol; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D002118:Calcium