title: HSPA2 overexpression protects V79 fibroblasts against bortezomib-induced apoptosis.
abstract: Human HSPA2 is a member of the HSPA (HSP70) family of heat-shock proteins, encoded by the gene originally described as testis-specific. Recently, it has been reported that HSPA2 can be also expressed in human somatic tissues in a cell-type specific manner. The aim of the present study was to find out whether HSPA2 can increase the resistance of somatic cells to the toxic effect of heat shock, proteasome inhibitors, and several anticancer cytostatics. We used a Chinese hamster fibroblast V79 cell line because these cells do not express the HSPA2 and cytoprotective HSPA1 proteins under normal culture conditions and show limited ability to express HSPA1 in response to heat shock and proteasome inhibitors. We established, by retroviral gene transfer, a stable V79/HSPA2 cell line, which constitutively overexpressed HSPA2 protein. The major observation of our study was that HSPA2 increased long-term survival of cells subjected to heat shock and proteasome inhibitors. We found, that HSPA2 confers resistance to bortezomib-induced apoptosis. Thus, we showed for the first time that in somatic cells HSPA2 can be a part of a system protecting cells against cytotoxic stimuli inducing proteotoxic stress.
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Piotr Teodor
authors.initials: PT
authors.lastname: Filipczak
authors.forename: Wojciech
authors.initials: W
authors.lastname: Piglowski
authors.forename: Magdalena
authors.initials: M
authors.lastname: Glowala-Kosinska
authors.forename: Zdzislaw
authors.initials: Z
authors.lastname: Krawczyk
authors.forename: Dorota
authors.initials: D
authors.lastname: Scieglinska
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival; D058639:Cold-Shock Response; D006224:Cricetinae; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D013312:Stress, Physiological
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D015853:Cysteine Proteinase Inhibitors; D018840:HSP70 Heat-Shock Proteins; C091879:HSPA2 protein, human; D007976:Leupeptins; D011719:Pyrazines; D011994:Recombinant Proteins; D000069286:Bortezomib; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde