Bcl-2 inhibits p53 nuclear import following DNA damage

Beham, A.; Marin, Maria C; Fernández, Ariel; Herrmann, John L.; Brisbay, Shawn; Tari, Ana M.; López-Berestein, Gabriel; Lozano, Guillermina; Sarkiss, Mona; McDonnell, Timothy J.

doi:10.1038/sj.onc.1201464

Cited by 84 publications

(51 citation statements)

References 27 publications

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“…RT4 was used as a positive control because we have demonstrated, using antisense, that Bcl-2 protects against drug-induced apoptosis in this cell type (Arriola, manuscript in preparation). Recently, Bcl-2 has been shown to inhibit translocation of p53 to the nucleus and this has been suggested to be important for function (Beham et al, 1997). However, we did not ®nd this to be the case in either RT4, where Bcl-2 inhibits apoptosis ( Figure 3i) or in 833K.Bcl-2 clones, where Bcl-2 promotes apoptosis ( Figure 3f).…”

Section: Overexpression Of Bcl-2 Enhances Etoposide-induced Apoptosiscontrasting

confidence: 46%

Bcl-2 overexpression results in reciprocal downregulation of Bcl-XL and sensitizes human testicular germ cell tumours to chemotherapy-induced apoptosis

et al. 1999

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Testicular germ cell tumours are hypersentive to chemotherapy and cell lines derived from these tumours are chemosensitive in vitro. We have previously shown that these cell lines express undetectable levels of the suppressor of apoptosis Bcl-2 and relatively high levels of the apoptosis inducer Bax (Chresta et al., 1996). To determine whether the absence of Bcl-2 in these cell lines makes them highly susceptible to drug-induced apoptosis, Bcl-2 was expressed ectopically in the 833K testicular germ cell tumour cell line. Stable overexpressing clones were isolated and three clones were studied further. Surprisingly, Bcl-2 overexpressing cells were sensitized to chemotherapy-induced apoptosis compared to the parental and vector control cells. Analysis of potential mechanisms of sensitization revealed there was a reciprocal downregulation of the endogenously expressed Bcl-X L in the Bcl-2 overexpressing clones. Downregulation of Bcl-X L to the same extent using antisense oligonucleotides enhanced etoposide-induced apoptosis by twofold. Our results indicate that Bcl-2 and Bcl-X L have dierent abilities to protect against chemotherapyinduced apoptosis in testicular germ cell tumours. In contrast to ®ndings in some tumour cell types, Bcl-2 did not act as a gatekeeper to prevent entry of p53 to the nucleus.

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Section: Overexpression Of Bcl-2 Enhances Etoposide-induced Apoptosiscontrasting

confidence: 46%

Bcl-2 overexpression results in reciprocal downregulation of Bcl-XL and sensitizes human testicular germ cell tumours to chemotherapy-induced apoptosis

et al. 1999

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“…Some studies have shown that RT decreases Bcl-2 protein expression in p53 wild-type cell lines, in conjunction with apoptotic cell death (26); p53 appears to down-regulate the expression of bcl-2 and transactivate bax (27). Moreover, Bcl-2 appears to inhibit the nuclear transport of p53 in response to genotoxic stress (28). In cell lines lacking wild-type p53 protein, bcl-2 expression may be up-regulated by RT (29).…”

Section: Discussionmentioning

confidence: 99%

Antisense Bcl-2 sensitizes prostate cancer cells to radiation

Hachem

Pollack

2005

Prostate

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BACKGROUND-Bcl-2 is anti-apoptotic and overexpression is associated with prostate tumor aggressiveness. We hypothesized that Bcl-2 has a role in prostate cancer radiation (RT) response. The relationship of Bcl-2 expression in four prostate cancer cell lines, and the effect of modulating expression with a Bcl-2 antisense oligonucleotide (G3139, Genasense ® , oblimersen sodium, Genta Incorporated), to RT was examined.

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“…The failure of bcl-2 to protect against prostate carcinoma cell death induction resulting from inhibition of proteasomal activity is noteworthy in that bcl-2 expression has been shown to confer resistance to prostate cell death induction by divergent stresses including g-radiation, p53, ceramide, inhibitors of arachidonate metabolism, TNF-a, and androgen deprivation in an orthotopic animal model system (Beham et al, 1997;Herrmann et al, 1997a,b;Tu et al, 1995;Westin et al, 1997). Several possibilities might account for the inability of bcl-2 to protect against proteasome inhibitors.…”

Section: Discussionmentioning

confidence: 99%