A recombinant bcl-x s adenovirus selectively induces apoptosis in cancer cells but not in normal bone marrow cells.

Clarke, Michael F.; Apel, Ingrid J.; Benedict, Mary A.; Eipers, Peter; Sumantran, Venil N.; González-Garcı́a, Maribel; Doedens, Monica; Fukunaga, Nina; Davidson, Beverly L.; Dick, John E.; Minn, Andy J.; Boise, Lawrence H.; Thompson, Craig B.; Wicha, Max S.; Núñez, Gabriel

doi:10.1073/pnas.92.24.11024

Cited by 126 publications

(83 citation statements)

References 30 publications

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“…This may explain why it was possible to purge malignant cells from the bone marrow without toxicity to clonogenic progenitor by using an adenovirus containing the Bcl-xs cDNA driven by the RSV promoter. 37 Our study demonstrates that the CMV E1a and MSCV promoters function efficiently in human hematopoietic stem cells; an observation that is consistent with other reports. 20,23,31 Indeed, adenoviral vectors in which the ecotropic receptor gene is under the control of the CMV promoter resulted in significantly higher transduction frequencies with a reciprocal increase in the transduction of the CD34 + cells and the clonogenic hematopoietic progenitors with ecotropic retroviral vectors.…”

Section: Figure 7 Sequential Transduction Of the Cd34 + Cd38 − Cells supporting

confidence: 92%

Adenovirus-mediated expresssion of the murine ecotropic receptor facilitates transduction of human hematopoietic cells with an ecotropic retroviral vector

et al. 1999

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One factor limiting the ability to modify human repopulating to 48%) by replacing the RSV promoter with the CMV E1a hematopoietic cells genetically with retroviral vectors is the promoter, resulting in a parallel increase in retroviral transrelatively low expression of the cognate viral receptor. We duction efficiency. Replacing the head portion of the fiber have tested sequential transduction of human hematopoprotein in conventional adenoviral vectors (serotype 5) with ietic cells with an adenoviral vector encoding the ecotropic the corresponding portion from an adenoviral 3 serotype retroviral receptor followed by transduction with an ecoresulted in ecotropic receptor expression in 60% of CD34 + tropic retroviral vector. Adenoviral transduction of K562 cells at an MOI of 10 4 and a retroviral transduction of 60% erythroleukemia cells was highly efficiently with Ͼ95% of of hematopoietic clonogenic progenitors. The sequential cells expressing the ecotropic receptor at a multiplicity of transduction strategy also resulted in efficient transduction infection (MOI) of 10 3 with a correspondingly high transof the primitive CD34 + CD38 − subset suggesting that it may duction with a retroviral vector. Ecotropic receptor hold promise for genetic modification of human hematopoexpression in CD34 + cells following transduction with adenietic stem cells. oviral vectors was increased by at least two-fold (from 20

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Section: Figure 7 Sequential Transduction Of the Cd34 + Cd38 − Cells supporting

confidence: 92%

Adenovirus-mediated expresssion of the murine ecotropic receptor facilitates transduction of human hematopoietic cells with an ecotropic retroviral vector

et al. 1999

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“…Therefore, in order to understand the apoptotic mechanism of action of this family of proteins, it is important to study and compare the mechanisms of action of di erent family members. One such protein, Bcl-x S , has been implicated in apoptosis induced by various stimuli in several tissues and cancer cells (see, e.g., Clarke et al, 1995). In the present study we therefore investigated the mechanism of action of Bcl-x S in apoptosis of PC12 cells (a cancer cell line commonly used for the study of neuronal apoptosis) and compared it to that of Bax.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, transient expression of Bcl-x S by infection with adenovirus vector containing bcl-x S cDNA was found to induce apoptosis in various cancer cells, suggesting that targeting of Bcl-x S expression into cancer cells may be a useful therapeutic approach of killing these cells (Clarke et al, 1995;Ealovega, 1996;Dole et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Bcl-xS and Bax induce different apoptotic pathways in PC12 cells

2000

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“…However, such a model would be inconsistent with our ®nding that a pro-death protein (bcl-XS) caused redistribution of cells from S to G1 phase of the cell cycle unless one considers the fact that bcl-XS is a rather unique pro-death protein. Bcl-XS shares properties of both the pro-and anti-death members of the bcl-2 family: it has a BH4 domain (indicative of anti-apoptotic members), yet it has been shown (when expressed at supraphyisological levels) to induce or sensitize cells to die (Minn et al, 1996b;Sumantran et al, 1995;Clarke et al, 1995;Dole et al, 1996;Ealovega et al, 1996;Boise et al, 1993;Ray et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Expression of Bcl-XS alters cytokinetics and decreases clonogenic survival in K12 rat colon carcinoma cells

Fridman

Rehemtulla

Hofmann³

et al. 1998

Oncogene

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bcl-XS, a member of the bcl-2 family, has been shown to induce and/or sensitize some cells to undergo programmed cell death, and to negate the anti-apoptotic activity of bcl-XL and bcl-2 by mechanisms which are still uncertain. To help understand these mechanisms we have established stable derivatives of the K12 rat colon carcinoma cell line that express bcl-XS in a tetracyclineregulated manner, using an autoregulatory retroviral cassette. When bcl-XS expression is induced, we observe two phenotypic responses. A small fraction of cells appear to undergo spontaneous apoptosis while the majority of cells undergo a form of cytostasis. In the latter case, the cells stop dividing (or divide a limited number of times at a retarded rate) and swell to many times their original size. These cells can take on a ghostlike appearance and subsequently detach from the culture plates and die or they may remain intact in a hindered state of proliferation. Doubling times were calculated to be 31.4 h in the presence of tetracycline and 50.4 h without tetracycline, bcl-XS expression also causes dramatic alterations in the cell cycle distribution of K12 cells manifesting as a substantial decrease (&50%) in the fraction of S phase cells with a concomitant increase in the G1 population. Continuous expression of bcl-XS, at levels approximately equal to that of bcl-XL, decreased the viability of K12 cells as demonstrated by a log decline in clonogenic survival. This decrease occurred without considerable apoptosis or a compensatory increase in the level of bcl-XL. None of these phenotypes were present in control cells expressing b-galactosidase in a similar retroviral cassette. These observations demonstrate that bcl-XS can have substantial cytokinetic e ects under circumstances that produce relatively little apoptosis.

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A recombinant bcl-x s adenovirus selectively induces apoptosis in cancer cells but not in normal bone marrow cells.

Cited by 126 publications

References 30 publications

Adenovirus-mediated expresssion of the murine ecotropic receptor facilitates transduction of human hematopoietic cells with an ecotropic retroviral vector

Adenovirus-mediated expresssion of the murine ecotropic receptor facilitates transduction of human hematopoietic cells with an ecotropic retroviral vector

Bcl-xS and Bax induce different apoptotic pathways in PC12 cells

Expression of Bcl-XS alters cytokinetics and decreases clonogenic survival in K12 rat colon carcinoma cells

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