Irradiation induces G2/M cell cycle arrest and apoptosis in p53-deficient lymphoblastic leukemia cells without affecting Bcl-2 and Bax expression

Strasser-Wozak, Elisabeth Mc; Hartmann, Bernd L.; Geley, Stephan; Sgonc, Roswitha; Böck, Günther; Santos, Antonio J Oliveira Dos; Hattmannstorfer, Rosa; Wolf, H.; Pavelka, Margit; Kofler, Reinhard

doi:10.1038/sj.cdd.4400402

Cited by 41 publications

(29 citation statements)

References 26 publications

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“…As previously reported, results indicate a progressive G2/M accumulation after radiation (Muschel et al, 1998), an effect which could be linked to the loss of p53 function (Haas-Kogan et al, 1995;Strasser-Wozak et al, 1998). Even though pRb2/p130 overexpression induced a G0/G1 accumulation, the irradiation-dependent accumulation in G2/M became significantly more evident over time.…”

Section: G-radiation-induced Apoptosis In Hjc12 Cell Line Is Enhancedsupporting

confidence: 63%

pRb2/p130 promotes radiation-induced cell death in the glioblastoma cell line HJC12 by p73 upregulation and Bcl-2 downregulation

et al. 2002

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This study shows that in the glioblastoma hamster cell line HJC12 the retinoblastoma family member pRb2/ p130 enhances g-radiation-induced cell death. In HJC12 cells the tetracycline-regulated expression of pRb2/p130 increased the percentage of g-radiation-induced apoptotic cells from 27 to 47%. pRb2/p130 overexpression was associated with the downregulation of the anti-apoptotic factor Bcl-2 and the upregulation of the steady-state protein levels of the pro-apoptotic transcription factor p73. In particular, RT -PCR showed a significant increase in the expression of the p73d isoform when pRb2/p130 was overexpressed. The ability of pRb2/p130 to modulate apoptosis was not associated with its role in mediating G0/G1 arrest during cell cycle progression. Our data suggest a role for pRb2/p130 in glioblastoma g-radiation-induced cell death, indicating that the antitumoral action of pRb2/p130 can regulate both inhibition of cell cycle progression and induction of cell death.

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Section: G-radiation-induced Apoptosis In Hjc12 Cell Line Is Enhancedsupporting

confidence: 63%

pRb2/p130 promotes radiation-induced cell death in the glioblastoma cell line HJC12 by p73 upregulation and Bcl-2 downregulation

et al. 2002

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“…In contrast, the lack of p53 favored an increase of cells in G2/M phase. Therefore, these data suggest that p53 mediates a G1 arrest in neural progenitors and also that a secure mechanism of cell cycle arrest occurring in G2/ M phase would be regulated by p53-independent pathways as shown in many cell lines (Strasser-Wozak et al, 1998;Matsui et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Involvement of p53 and Fas/CD95 in murine neural progenitor cell response to ionizing irradiation

et al. 2004

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We investigated the role of tumor suppressor p53 and Fas (CD95/APO-1), a member of the tumor necrosis factor receptor family, in neural progenitors response to cirradiation exposure. Telencephalic cells were obtained from wild-type C57Bl/6, or p53À/À or fasÀ/À, 15-dayold mouse embryos. They were cultured in conditions allowing neural progenitors to form proliferating clusters (neurospheres). A 2 Gy c-irradiation induced a G1 cell cycle arrest and triggered apoptosis in wild-type neural progenitor cultures in correlation with an enhanced expression of p53 and of its downstream target p21 WAF1 , both of them acquiring a nuclear localization. These effects did not occur in p53À/À neural progenitors demonstrating the central role played by p53 in their response to ionizing radiation. Furthermore, the monoclonal antibody Jo2 directed against Fas induced apoptosis of wild type but not of fasÀ/À neural progenitors, indicating the existence of a functional Fas signaling pathway in neural progenitors. Ionizing radiation induced an increase of Fas membrane expression related to a p53-dependent increase of fas mRNA expression in wild-type neural progenitors. Moreover, fasÀ/À neural progenitors exhibited delayed radiation-induced apoptosis compared to wild-type cells. Therefore, these findings establish a role for Fas/CD95 related to p53 in the response of neural progenitors to c-radiation exposure. Similar mechanisms could be triggered in neural progenitors in case of different stresses during brain development or in the course of various diseases affecting the adult brain.

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“…35 Thus, we would like to suggest that the arrested replication machinery with stalled replication forks provides the primary signal which in certain cell types results in apoptosis induction. However, in the investigated cell line the mechanism cannot be a generic DNA strandbreak-induced apoptosis, as it was shown in our previous studies that strandbreak-induced apoptosis in CEM-C7H2 cells triggered by X-rays 36 or doxorubicin 37 caused accumulation of cells and apoptosis in the G2-phase of the cell cycle. Nonetheless, it is conceivable that resveratrol-induced apoptosis is triggered by a different type of DNA lesion.…”

Section: Cell Death and Differentiationmentioning

confidence: 99%

Resveratrol causes arrest in the S-phase prior to Fas-independent apoptosis in CEM-C7H2 acute leukemia cells

et al. 2000

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Resveratrol (3,5,4'-trihydroxy-trans-stilbene), in the concentration range of 20 mM and above, induced arrest in the Sphase and apoptosis in the T cell-derived T-ALL lymphocytic leukemia cell line CEM-C7H2 which is deficient in functional p53 and p16. Expression of transgenic p16/INK4A, which causes arrest in G0/G1, markedly reduced the percentage of apoptotic cells. Antagonist antibodies to Fas or FasL, or constitutive expression of crmA did not diminish the extent of resveratrol-induced apoptosis. Furthermore, a caspase-8-negative, Fas-resistant Jurkat cell line was sensitive to resveratrol-induced apoptosis which could be strongly inhibited in the Jurkat as well as in the CEM cell line by z-VAD-fmk and z-IETD-fmk. The almost complete inhibition by z-IETD-fmk and the lack of inhibition by crmA suggested caspase-6 to be the essential initiator caspase. Western blots revealed the massive conversion of procaspase-6 to its active form, while caspase-3 and caspase-2 were proteolytically activated to a much lesser extent. Cell Death and Differentiation (2000) 7, 834 ± 842.

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Irradiation induces G2/M cell cycle arrest and apoptosis in p53-deficient lymphoblastic leukemia cells without affecting Bcl-2 and Bax expression

Cited by 41 publications

References 26 publications

pRb2/p130 promotes radiation-induced cell death in the glioblastoma cell line HJC12 by p73 upregulation and Bcl-2 downregulation

pRb2/p130 promotes radiation-induced cell death in the glioblastoma cell line HJC12 by p73 upregulation and Bcl-2 downregulation

Involvement of p53 and Fas/CD95 in murine neural progenitor cell response to ionizing irradiation

Resveratrol causes arrest in the S-phase prior to Fas-independent apoptosis in CEM-C7H2 acute leukemia cells

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