The effects of JNK isoform knockdown on cell growth and death in HUVECs and MCF-7 cells

  • Rachel Aimee Wood

Student thesis: Doctoral Thesis

Abstract

Cardiovascular disease (CVD) and cancer are two of the leading causes of mortality worldwide. The JNK pathway has been shown to play key roles at various stages of both of these diseases and therefore is an important protein to try and understand. In animal models of atherosclerosis and breast cancer, inhibition of JNK has been demonstrated to reduce pathogenesis and therefore targeting this protein may be key for developing treatments. JNK exists as three individual proteins, JNK1, JNK2 and JNK3 and studies are now showing that not only can these proteins work independently but also opposingly in some instances and therefore understanding the function of the individual isoforms is becoming critical to fully understanding this pathway. Although more research is focusing on JNK isoform function, characterisation of each JNK protein has not yet been carried out in human primary vascular cells or a human breast cancer cell line, an investigation which must be carried out to understand the role of this pathway in the pathogenesis of these diseases. In the current study lentiviral shRNA was used to target and knockdown JNK1 and JNK2 in both human umbilical vein endothelial cells (HUVECs) and MCF-7 breast cancer cells and the effects of knockdown on cell growth and cell death processes were analysed. In HUVECs knockdown of JNK2 caused an increase in pc-Jun levels and an increase in the percentage of multinucleated cells was observed, suggesting JNK2 may play a role in HUVEC cell growth. Unfortunately, the lentiviral infection itself caused detrimental effects which made it difficult to continue experiments and explore these findings further. In MCF-7 cells JNK knockdown did not produce any changes in cell growth or induced cell death when compared to non-target controls, suggesting that JNK does not play a key role in this breast cancer cell line.
Date of Award1 Oct 2016
LanguageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsUniversity of Strathclyde
SupervisorRobin Plevin (Supervisor) & Andrew Paul (Supervisor)

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