Investigating the functions of the c-Jun and JunB transcription factors in classical Hodgkin Lymphoma

• Author / Creator

  Zhang, Jing Xi

• Classical Hodgkin lymphoma (cHL) is characterized by the presence of abnormal mononuclear Hodgkin and multinuclear Reed-Sternberg (HRS) cells, which are thought to be derived from clonally expanded germinal center B cells. The tumour cells have been demonstrated to have various signalling pathways being dysregulated to promote cell proliferation and survival. Among the deregulated pathways, the activator protein-1 (AP-1) signalling pathway, which consists of a family of transcription factors has been implicated in promoting cell proliferation and is involved in regulating immune evasion in cHL. However, very few studies have been conducted on the specific role of each AP-1 member, particularly the two aberrantly expressed AP-1 proteins, c-Jun and JunB, in the pathogenesis of cHL. We used a shRNA-mediated gene silencing approach to specifically knock down c-Jun and JunB protein in cHL cell lines and examined the effect on proliferation and apoptosis. We found that knocking down either protein reduced proliferation rate and resulted in a prolonged G0/G1 phase compared to control shRNA-expressing cells. Moreover, knocking down c-Jun or JunB did not significantly affect the apoptosis rate in cHL cell lines. We further examined their function in tumour growth in vivo and observed a similar smaller tumour formed with cells expressing either c-Jun or JunB shRNA compared to control group. Interestingly, the c-Jun and JunB knockdown cells within cell lines shared similarities in proliferation and cell cycle defect suggesting the two AP-1 proteins may have some similar functions in cHL. In addition, we examined the transcriptional profile of the two AP-1 proteins by doing microarrays in order to understand the cellular function of c-Jun and JunB in cHL. We found the two proteins shared many common targets within each cell line and they influenced many genes involved in inflammatory response, proliferation, and apoptosis. The results of this study provide insight into the genes and cellular functions regulated by c-Jun and JunB in cHL and the increased knowledge of the roles of these proteins may eventually lead to the development of novel targets for treatment.

• Subjects / Keywords

  • AP-1
  • C-Jun
  • Classical Hodgkin lymphoma
  • JunB

• Graduation date

  Fall 2016

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3ST7F73W

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.