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The Role of Cyclin D1 in the Chemoresistance of Mantle Cell Lymphoma

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Technical Report,01 Sep 2016,31 Aug 2017

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City of Hope Beckman Research Institute Duarte United States

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Mantle cell lymphoma MCL is an aggressive B-cell malignancy characterized by over-expression of the cell cycle regulatory protein cyclin D1 CCND1. Increased CCND1 expression levels are strongly associated with shorter patient survival related to chemoresistance, but little is known about the contribution of CCND1 to the resistant nature of MCL. On the basis of our preliminary data, we hypothesize that cyclin D1 plays a genome protective role through regulating expression of CDK5RAP3 C53, which encodes a putative tumor suppressor known to antagonize the DNA checkpoint kinase CHEK1. We test this hypothesis by focusing on the following specific aims 1 determine the effect of C53 depletion or overexpression on CCND1 knockdown phenotypes 2 determine the role of CCND1 in regulating C53 expression. This report describes additional results from specific aim 1 and partial results from specific aim 2. We have found that C53 overexpression increases DNA damage in CCND1-depleted MCL cells, but is not sufficient to affect ATR and CHEK1 signaling. In addition, using a C53 reporter assay, we found that CCND1 can directly interact with and negatively regulate C53 promoter activity.

Subject Categories:

  • Biochemistry
  • Genetic Engineering and Molecular Biology
  • Medicine and Medical Research

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