title: Induction of heat shock protein HSPA6 (HSP70B') upon HSP90 inhibition in cancer cell lines.
abstract: Genome-wide transcript profiling to elucidate responses to HSP90 inhibition revealed strong induction of HSPA6 in MCF-7 cells treated with 17-AAG. Time- and dose dependent induction of HSPA6 (confirmed by qPCR and Western Blots) occurred also upon treatment with Radicicol, another HSP90 inhibitor. HSPA6 was not detectable in untreated cells or cells treated with toxins that do not inhibit HSP90, or upon applying oxidative stress. Thus, HSPA6 induction is not a general response to cytotoxic insults. Modulation of HSPA6 levels by siRNA-mediated inhibition or recombinant expression did not influence 17-AAG mediated cell death. HSPA6 induction as a consequence of HSP90 inhibition occurs in various (but not all) cell lines and may be a more specific marker for HSP90 inhibition than induction of other HSP70 proteins.
authors.affiliation: Roche Pharma Research & Early Development, Large Molecule Research, Roche Innovation Center Penzberg, Nonnenwald 2, 82377 Penzberg, Germany. Electronic address: petric.kuballa@roche.com.
authors.forename: Petric
authors.initials: P
authors.lastname: Kuballa
authors.affiliation: Roche Pharma Research & Early Development, Large Molecule Research, Roche Innovation Center Penzberg, Nonnenwald 2, 82377 Penzberg, Germany.
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Baumann
authors.affiliation: Roche Pharma Research & Early Development, Large Molecule Research, Roche Innovation Center Penzberg, Nonnenwald 2, 82377 Penzberg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Mayer
authors.affiliation: Roche Pharma Research & Early Development, Discovery Oncology, Roche Innovation Center Penzberg, Nonnenwald 2, 82377 Penzberg, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Bär
authors.affiliation: Roche Pharma Research & Early Development, Discovery Oncology, Roche Innovation Center Penzberg, Nonnenwald 2, 82377 Penzberg, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Burtscher
authors.affiliation: Roche Pharma Research & Early Development, Large Molecule Research, Roche Innovation Center Penzberg, Nonnenwald 2, 82377 Penzberg, Germany. Electronic address: ulrich.brinkmann@roche.com.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Brinkmann
mesh_terms: D000595:Amino Acid Sequence; D016227:Benzoquinones / Q000494:pharmacology; D015153:Blotting, Western; D020126:Brefeldin A / Q000494:pharmacology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D056945:Hep G2 Cells; D006358:Hot Temperature; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D061986:MCF-7 Cells; D018942:Macrolides / Q000494:pharmacology; D008969:Molecular Sequence Data; D034622:RNA Interference; D017386:Sequence Homology, Amino Acid; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics*
chemical_list: D016227:Benzoquinones; D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C544598:HSPA6 protein, human; D047029:Lactams, Macrocyclic; D007976:Leupeptins; D018942:Macrolides; D020126:Brefeldin A; C112765:tanespimycin; D019284:Thapsigargin; C035359:monorden; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
keywords: Cancer therapy; Geldanamycin; Heat shock response; Oxidative stress; Radicicol; Unfolded protein response