Hsp27 overexpression inhibits doxorubicin-induced apoptosis in human breast cancer cells.
Previously we demonstrated that heat shock protein 27 (hsp27) overexpression confers resistance to the chemotherapeutic agent doxorubicin in MDA-MB-231 breast cancer cells. Since induction of apoptosis is one underlying mechanism of chemotherapeutic drug action, we investigated the effect of hsp27 overexpression on doxorubicin-induced apoptosis, finding that hsp27 protects MDA-MB-231 cells from apoptosis. We also examined expression of the doxorubicin target, topoisomerase II (topo II), in control and hsp27-overexpressing stable transfectants, as topo II expression is important for both drug sensitivity and the initiation of apoptosis by doxorubicin. The relative levels of both topo IIalpha and beta were higher in the controls than the hsp27-overexpressing clones, suggesting that the apoptotic protective effect of hsp27 overexpression in MDA-MB-231 cells is associated with altered topo II expression.
Hansen
R K
RK
Department of Medicine, The University of Texas Health Science Center, San Antonio, USA.
Parra
I
I
Lemieux
P
P
Oesterreich
S
S
Hilsenbeck
S G
SG
Fuqua
S A
SA
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002999:Clone Cells; D053938:DNA Fragmentation; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis; D004268:DNA-Binding Proteins; D004317:Doxorubicin / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D059005:Topoisomerase II Inhibitors; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D007527:Isoenzymes; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D059005:Topoisomerase II Inhibitors; D004317:Doxorubicin; D004250:DNA Topoisomerases, Type II