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Home › Dataset Library › A Novel Pro-Survival Function of Cyclin-D1 Underlies Its Oncogenic Role and Potential as a Therapeutic Target in Human and Murine Mantle...

Dataset: A Novel Pro-Survival Function of Cyclin-D1 Underlies Its Oncogenic Role and Potential as a Therapeutic Target in Human and Murine Mantle Cell Lymphoma

The chromosomal translocation t(11;14)(q13;q32) leading to cyclin-D1 over-expression plays an essential role in the development of mantle...

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The chromosomal translocation t(11;14)(q13;q32) leading to cyclin-D1 over-expression plays an essential role in the development of mantle cell lymphoma (MCL), an aggressive tumor that remains incurable with current therapies. Cyclin-D1 has been postulated as an effective therapeutic target, but its evaluation has been hampered by our incomplete understanding of its oncogenic functions and by the lack of valid MCL murine models. To address these issues, we generated a cyclin-D1-driven mouse model whereby cyclin-D1 expression can be externally regulated. These mice developed lymphomas capable of recapitulating most features of human MCL. We found that cyclin-D1 inactivation was not sufficient to induce lymphoma regression in vivo. However, using a combination of in vitro and in vivo assays, we identified a novel pro-survival cyclin-D1 function in MCL cells. Specifically, we demonstrate that cyclin-D1 sequestrates the pro-apoptotic protein BAX, thereby favoring BCL2 anti-apoptotic function. Accordingly, cyclin-D1 inhibition sensitized the lymphoma cells to apoptosis through BAX release. Thus, genetic or pharmacologic targeting of cyclin-D1 combined with a pro-apoptotic BH3 mimetic synergistically killed murine lymphomas and human MCL cells. Our study identifies a novel role of cyclin-D1 in deregulating apoptosis and highlights the potential benefit of simultaneously targeting cyclin-D1 and survival pathways in patients with MCL. Dose response involving 20 samples. Two replicates for each cell line, 4 cell lines sensitive to ABT-737 and 6 cell lines resistant to ABT-737. Mantel cell lymphoma cell lines sensitive to ABT-737 vs. Mantel cell lymphoma cell lines resistant to ABT-737

Species:
human

Samples:
20

Source:
E-GEOD-25613

Updated:
Dec.12, 2014

Registered:
Sep.15, 2014


Factors: (via ArrayExpress)
Sample CELL LINE
GSM629484 G519
GSM629484 G519
GSM629486 HBL2
GSM629486 HBL2
GSM629488 IRM2
GSM629488 IRM2
GSM629490 JEKO
GSM629490 JEKO
GSM629492 JVM2
GSM629492 JVM2
GSM629494 L128
GSM629494 L128
GSM629496 MINO
GSM629496 MINO
GSM629498 REC1
GSM629498 REC1
GSM629500 UPN1
GSM629500 UPN1
GSM629502 Z138
GSM629502 Z138

Tags

  • cell
  • line
  • lymphoma
  • mantle cell lymphoma
  • protein

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