Selective depletion of heat shock protein 70 (Hsp70) activates a tumor-specific death program that is independent of caspases and bypasses Bcl-2

Nylandsted, Jesper; Rohde, Mikkel; Brand, Karsten; Bastholm, Lone; Elling, Folmer; Jäättelä, Marja

doi:10.1073/pnas.97.14.7871

Cited by 364 publications

(290 citation statements)

References 46 publications

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“…5 The ability of such proteins to prevent apoptosis induced by several anticancer drugs also explains how these proteins could limit the efficacy of cancer therapy. 6,7 Indirect experimental evidence and clinical-pathological studies indicate that HSP70 is the major stress inducible, cancerassociated, antiapoptotic protein. 4 Increased expression of HSP70 has been reported in high grade malignant breast and endometrial tumors, osteosarcoma and renal cell tumors.…”

mentioning

confidence: 99%

Retracted: Heat‐shock pretreatment inhibits sorbitol‐induced apoptosis in K562, U937 and HeLa cells

Marfè

Pucci

Martino

et al. 2009

Intl Journal of Cancer

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The aim of this study was to determine whether heat-shock pretreatment exerted a protective effect against sorbitol-induced apoptotic cell death in K562, U937 and HeLa cell lines and whether such protection was associated with a decreased cytochrome c release from mithocondria and a decreased activation of caspase-9 and -3. Following heat-shock pretreatment (42 6 0.3°C for 1 hr), these cell lines were exposed to sorbitol for 1 hr. Apoptosis was evaluated by DNA fragmentation, whereas caspase-9,-3 activation, cytochrome c release and heat-shock protein70 (HSP70) were assayed by Western Blot. Sorbitol exposure-induced apoptosis in these different cell lines with a marked activation of caspase-9 and caspase-3, whereas heat-shock pretreatment before sorbitol exposure, induced expression of HSP70 and inhibited sorbitol-mediated cytochrome c release and subsequent activation of caspase-9 and caspase-3. Similarly, overexpression of HSP70 in the three cell lines studied prevented caspase-9 cleavage and activation as well as cell death. Furthermore, we showed that the mRNA expression of iNOS decreased during both the heat-shock treatment and heat-shock pretreatment before sorbitol exposure. By contrast, the expression of Cu-Zn superoxide dismutase (SOD) and Mn-SOD proteins increased during heat-shock pretreatment before sorbitol exposure. We conclude that, heat-shock pretreatment protects different cell lines against sorbitol-induced apoptosis through a mechanism that is likely to involve SOD family members. ' 2009 UICC

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mentioning

confidence: 99%

Retracted: Heat‐shock pretreatment inhibits sorbitol‐induced apoptosis in K562, U937 and HeLa cells

Marfè

Pucci

Martino

et al. 2009

Intl Journal of Cancer

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“…The most significant finding was the compaction and marginalisation of chromatin at the nuclear periphery, which is a cytological hallmark of apoptosis (Kerr et al, 1995). Similar changes have been observed during apoptotic cell death in MCF-7 cells transfected with antisense Hsp70 cDNA (Nylandsted et al, 2000).…”

Section: Discussionsupporting

confidence: 56%

Inhibition of growth and induction of apoptosis in human breast cancer by transfection of gef gene

et al. 2003

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The gef gene has cell-killing functions in Escherichia coli. To evaluate the feasibility of using this gene as a new strategy for cancer therapy, we transfected it in MCF-7 cells derived from breast cancer (MCF-7TG). The gef gene was cloned in a pMAMneo vector under the control of a mouse mammary tumour virus promoter, inducible by dexamethasone (Dex), and was transfected with liposomes. After selection and induction, expression of the gef gene was confirmed by reverse transcription -polymerase chain reactions (RT -PCR) and Western blot. Cell viability was determined with a haemocytometre and the sulphorodamine B colorimetric assay, and the cell cycle was studied by propidium iodide (PI) staining. Annexin V-FITC and PI assays were used to evaluate apoptosis, which was confirmed by electron microscopy. In comparison with MCF-7 parental cells and MCF-7 cells transfected with an empty vector, MCF-7TG cells induced with Dex showed a significant decrease in proliferation rate, which was associated with evidence of apoptosis. Morphological findings confirmed apoptosis and showed a typical pattern of mitochondrial dilation. Furthermore, the cell cycle was characterised by premature progression from G 1 to S phase and G 2 delay. Our results show that the gef gene was able to decrease proliferation in a breast cancer cell line, and induce apoptosis. These findings suggest that the gef gene is a potential candidate for tumour therapy.

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“…Moreover, HSP70 and other heat shock proteins can inhibit caspase-dependent and -independent apoptotic stimuli and they can confer immortality to cells of different types (Nylandsted et al, 2000). Both HSP70 and HSP90 block Apaf-1 complex formation and consequently the activation of caspase-9 (Beere et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Senescence‐associated HSP60 expression in normal human skin fibroblasts

et al. 2005

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Normal mammalian fibroblasts cultured in vitro undergo a limited number of divisions before entering a senescent phase in which they can be maintained for long periods but cannot be induced to divide. Senescent cells become unresponsive to growth-promoting signals and exhibit senescent cell morphology with flattened and enlarged cell shape. Several chaperones have a direct effect on cellular senescence. HSP60 has been largely studied in our laboratories and it has been associated with uncontrolled cell proliferation in tumor cells. Since senescence is firmly regulated during cell cycle progression, we wanted to investigate HSP60 protein level during cellular senescence. Our data show that HSP60 increases during the initial stage of senescence and that it is localized in cellular compartments, resembling mitochondria. An increase in HSP60 protein amount is associated with a cell cycle slow-down and it may have a role in cell cycle progression.

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Selective depletion of heat shock protein 70 (Hsp70) activates a tumor-specific death program that is independent of caspases and bypasses Bcl-2

Cited by 364 publications

References 46 publications

Retracted: Heat‐shock pretreatment inhibits sorbitol‐induced apoptosis in K562, U937 and HeLa cells

Retracted: Heat‐shock pretreatment inhibits sorbitol‐induced apoptosis in K562, U937 and HeLa cells

Inhibition of growth and induction of apoptosis in human breast cancer by transfection of gef gene

Senescence‐associated HSP60 expression in normal human skin fibroblasts

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