17β-Estradiol-induced Increases in Glucose-regulated Protein 78kD and 94kD Protect Human Breast Cancer T47-D Cells from Thermal Injury

Juliann G. Kiang；Irene D. Gist；George C. Tsokos

heat shock proteins ； Ca(superscript 2+) ； viability ； heat ； protein kinase C ； protein kinase A ； estrogen ； breast cancer

The Chinese Journal of Physiology

40卷4期（1997 / 12 / 01）

213 - 219

英文

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 17β-estradiol-treated T47-D cells, a human breast cancer cell line. Cells exposed to 17β-estradiol for 24-48 h displayed increased expression of glucose regulated protein 78kD (GRP-78) and 94kD (GRP-94), as shown by [(subscript 35)S]methionine incorporation and Western blotting experiments. The increase was time (5 h to 48 h)-dependent at 1 nM and 1 μM 17β-estradiol. Cells overexpressing GRP-78 and -94 after treatment with 17β-estradiol displayed resistance against heat shock (47℃ for 50 min)-induced death. Removal of external Ca(superscript 2+) or treatment of cells with BAPTA (a Ca(superscript 2+) chelator) did not alter the synthesis of GRP-78 and -94, suggesting that the 17β-estradiol effect on the synthesis of GRP-78 and -94 is Ca2+-independent. In addition, exposure of cells to 17β-estradiol up to 100 μM did not increase [Ca(superscript 2+)](subscript i), which further supports the view that the estrogen-induced GRPs are not regulated by [Ca(superscript 2+)](subscript i). Treatment with H89 (a protein kinase A inhibitor, 1 μM, 30 min) or GF-109203X (a protein kinase C inhibitor, 1 μM, 30 min) also did not change the GRP synthesis, indicating that protein kinase A and C are not involved in regulation of GRP synthesis.