Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Pathology

Supervisor

Dr. Chandan Chakraborty

2nd Supervisor

Dr. Lee-Cyn Ang

Joint Supervisor

Abstract

Due to the highly invasive nature of glioblastoma multiforme (GBM), one way to combat this disease is to focus on its mechanism of progression and on effectively inhibiting the signalling pathways that control cell proliferation. There is increasing evidence of the role of the MEK5-ERK5 pathway in cancer progression. However, there is a lack of studies investigating the role of ERK5 in glioblastoma and other brain tumours. Exploring the molecular mechanisms that advances glioblastoma cell proliferation may help in identifying potential therapeutic targets. This study examines the expression of ERK5 in GBM and other types and grades of brain tumours. In addition, this study determines whether there exist differences in ERK5 expression between tumour grades, higher vs lower grades, gender, and age. I hypothesize, that the expression of ERK5 positively correlates with higher grade brain tumour progression.

ERK5 expression was analyzed by immunohistochemistry in 69 brain tumour tissue samples and a brain tumour tissue microarray (TMA) containing 80 patient samples, The expression of ERK5 was examined using a microscope, and the immunohistochemical reactivity for ERK5 was evaluated and scored according to the percentage of staining. The data was then analyzed by statistical analysis.

This study shows that highly invasive brain tumours, such as GBM, display a high level of expression of ERK5. Furthermore, ERK5 expression appears to increase with advancing tumour stage. My data supports glioblastoma as one of the types of cancer that display abnormal MEK5/ERK5 signalling. Hence, indicating that targeting the MEK5/ERK5 pathway for future targeted therapies to combat glioblastoma may have some potential. However, there is still much that is unknown and has yet to be explored.


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