Bcl-2-independent Bcr–Abl-mediated resistance to apoptosis: protection is correlated with up regulation of Bcl-xL

Amarante-Mendes, Gustavo P.; McGahon, Anne J.; Nishioka, Walter K.; Afar, Daniel; Witte, Owen N.; Green, Douglas R.

doi:10.1038/sj.onc.1201664

Cited by 203 publications

(177 citation statements)

References 24 publications

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“…This is in agreement with our results showing the dramatic reduction of Bcl-x expression in Ba/F3D749 cells in absence of IL-3. Similarly, it has been shown that suppression of apoptosis mediated by Bcr-abl or v-abl was independent of Bcl-2 expression but was correlated with up-regulation of Bcl-x L (Amarente- Mendes et al, 1998;Chen et al, 1997). Altogether these results support our data that inhibition of Bcl-x by the dominant negative form of STAT5 coincide with an increase of apoptosis in Ba/F3 cells in absence of IL-3.…”

Section: Discussionsupporting

confidence: 91%

IL-3 dependent regulation of Bcl-xL gene expression by STAT5 in a bone marrow derived cell line

et al. 1999

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Section: Discussionsupporting

confidence: 91%

IL-3 dependent regulation of Bcl-xL gene expression by STAT5 in a bone marrow derived cell line

et al. 1999

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“…We have demonstrated, therefore, that Bcl-x L expression is important in protecting keratinocytes and epithelial cells from DNA damage-induced cell death. These results complement studies in leukemia cells and cardiac myocytes where it was demonstrated that Bcl-x L was important in protecting cells from death induced by cytokines or the chemotherapy drug staurosporine (Fujio et al, 1997;Amarante-Mendes et al, 1998).…”

Section: Discussionsupporting

confidence: 83%

“…Other studies using Bcl-x L antisense oligonucleotides have simply targeted the translational start codon without searching for an optimal target. Because of this less stringent approach, the previous Bcl-x L antisense inhibitors that have been described appear to be much less e ective than those used here and, as such, need to be used at very high concentrations to see an e ect (Pollman et al, 1998;Fujio et al, 1997;Amarante-Mendes et al, 1998). Our approach identi®ed one inhibitor (ISIS 16009) that hybridized within the coding region of the gene and functioned to potently reduce Bcl-x L expression.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Bcl-xL expression sensitizes normal human keratinocytes and epithelial cells to apoptotic stimuli

et al. 1999

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The epidermis is continually exposed to harmful mutagens that have the potential to cause DNA damage. To protect the skin from accumulating mutated cells, keratinocytes have developed a highly regulated mechanism of eliminating damaged cells through apoptosis. Bclx L is a well-described cell survival protein that when overexpressed in skin can protect keratinocytes from UV radiation-induced apoptosis. To begin to unravel the complex mechanisms that keratinocytes use to survive, we wanted to characterize the role of endogenous Bcl-x L in protecting cells from death. In this study, we describe the development and characterization of an antisense inhibitor to Bcl-x L . We show that this inhibitor reduces Bcl-x L RNA and protein in a concentration-dependent, sequence-speci®c manner. Furthermore, treatment of keratinocytes and epithelial cells with this inhibitor sensitizes these cells to UV-B radiation and cisplatinum treatment-induced apoptosis. Thus, these results o er direct evidence that Bcl-x L is critical in the protection of skin and epithelial cells from apoptosis and provide a basis for the role of Bcl-x L in keratinocyte and epithelial cell survival.

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“…5,9,12,13,26,29,35,36 Extensive work on the function of Bcl-2 and the strong structural similarities between Bcl-2 and Bcl-x L have led to studies demonstrating the important role of Bcl-x L in the negative regulation of apoptotic cell death. 7,8,12,21,[27][28][29]37 Overexpression of Bcl-x L has been shown in other cell systems to induce the development of resistance to chemotherapeutic agents.…”

Section: Discussionmentioning

confidence: 99%

Bcl‐X_L is a chemoresistance factor in human melanoma cells that can be inhibited by antisense therapy

Heere-Ress

Thallinger

Lucas

et al. 2002

Intl Journal of Cancer

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Malignant melanoma is a tumor that responds poorly to a variety of apoptosis-inducing treatment modalities, such as chemotherapy. The expression of genes that regulate apoptotic cell death plays an important role in determining the sensitivity of tumor cells to chemotherapeutic intervention. Bcl-x L is an antiapoptotic member of the Bcl-2 family and is universally expressed in human melanoma. To evaluate the Bcl-x L protein as a potential therapeutic target in melanoma, the influence of Bcl-x L expression levels on the chemoresistance of human melanoma cells was investigated. Overexpression of Bcl-x L in stably transfected human melanoma Mel Juso cells significantly reduced sensitivity to cisplatin-induced apoptosis (p < 0.05). In a parallel approach, reduction of Bcl-x L protein by specific AS oligonucleotide (ISIS 16009) treatment enhanced the chemosensitivity of Mel Juso cells by 62% compared to cells treated with MM control oligonucleotide (ISIS 16967) as well as chemotherapy-induced apoptosis. These data suggest that Bcl-x L is an important factor contributing to the chemoresistance of human melanoma. Reduction of Bcl-x L expression by AS oligonucleotides provides a rational and promising approach that may help to overcome chemoresistance in this malignancy.

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Bcl-2-independent Bcr–Abl-mediated resistance to apoptosis: protection is correlated with up regulation of Bcl-xL

Cited by 203 publications

References 24 publications

IL-3 dependent regulation of Bcl-xL gene expression by STAT5 in a bone marrow derived cell line

IL-3 dependent regulation of Bcl-xL gene expression by STAT5 in a bone marrow derived cell line

Inhibition of Bcl-xL expression sensitizes normal human keratinocytes and epithelial cells to apoptotic stimuli

Bcl‐X_L is a chemoresistance factor in human melanoma cells that can be inhibited by antisense therapy

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Bcl-2-independent Bcr–Abl-mediated resistance to apoptosis: protection is correlated with up regulation of Bcl-xL

Cited by 203 publications

References 24 publications

IL-3 dependent regulation of Bcl-xL gene expression by STAT5 in a bone marrow derived cell line

IL-3 dependent regulation of Bcl-xL gene expression by STAT5 in a bone marrow derived cell line

Inhibition of Bcl-xL expression sensitizes normal human keratinocytes and epithelial cells to apoptotic stimuli

Bcl‐XL is a chemoresistance factor in human melanoma cells that can be inhibited by antisense therapy

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Bcl‐X_L is a chemoresistance factor in human melanoma cells that can be inhibited by antisense therapy