UNIVERSITY OF CALGARY

UNIVERSITY OF CALGARY
ING3 Expression in Prostate Cancer and Its Association with ERG Gene Rearrangements
and Patient Outcome
by
Amal Ahmed Almami
A THESIS
SUBMITTED TO THE FACULTY OF GRADUATE STUDIES
IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE
DEGREE OF MASTER OF SCIENCE
MEDICAL SCIENCE DEPARTMENT
CALGARY, ALBERTA
JANUARY, 2014
© Amal Ahmed Almami 2014

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Abstract
ETS Related Gene (ERG) rearrangement is one of the most common genetic changes seen in
roughly about 50% of prostate cancer (PCA) cases. The inhibitor of growth family member 3
(ING3) is a member of the ING tumor suppressor family. The deregulation of ING3 expression
has been reported in various types of cancers. However, to date the role and function of ING3 in
PCA as well as its relationship to ERG gene rearrangement has not been studied. Our initial
observation from microarray expression profiling showed that ING3 was down-regulated in ERG
positive prostate cancer samples in comparison to ERG negative tumors. In this work, we
examined the expression and localization of ING3 in prostate cancer cell lines and tissue samples
and its association to clinical outcome. We documented a significant association between ERG
and ING3 and showed a significant association to the patients’ clinical outcome, thus
highlighting a potential role for ING3 in prostate cancer progression.

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Acknowledgements
First of all, I would like to thank Almighty God for giving me the help and patience I need to
proceed in this journey. Also, I would like to acknowledge the King of Saudi Arabia, King
Abdullah bin Abdul-Aziz, who has given me the opportunity for education abroad. It is also a
great pleasure to thank those who made this thesis possible:
I would like to express my sincere gratitude to my supervisor, Dr. Tarek Bismar, for allowing
me to pursue my graduate studies in his laboratory and for his expertise, support and advice. I
would like to express my special thanks to my co-supervisor Dr. Douglas Demetrick for his
valuable thoughts, advice and feedback which helped to keep me on track and to work at a
smooth pace.
I also extend my thanks to my thesis committee members, Dr. Karl Riabowol and Dr. Kiril
Trpkov, for their valuable comments and insightful suggestions. They have been extremely
helpful throughout the stages of my work. My thanks also go to Dr. Adnan Mansoor for donating
his time to serve as my internal examiner.
I would like to express my deepest thanks to the Faculty of Medicine and the Department of
Medical Science at the University of Calgary for their help and support during these past few
years, especially Dr. Janice Braun, Dr. Tara Beattie, Dr. Shirin Bonni and Ms. Kiran Pandher, for
their guidance and assistance throughout this program.
I would also like to thank all past and present members of Dr. Bismar’s laboratory: all
postdocs’ fellows, Drs. Lars, Ting, Ashraf, Shuhong, Samar, Manal, Adrian, and Teng, for
sharing their wealth of knowledge and training me in several techniques. Also, thank you to

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Mike, Mohamed, Youjin, Ms. Maggie, Ms. Lori and Ms. Sze for the enjoyable group work and
stimulating discussions. Special appreciation to Dr. Shoraf Dadakhujaev and Dr. Susie Rosales
with whom I have enjoyed the many discussions we have had about science and life. I also
extend my thanks to Claude Veillette from Dr. Demetrick’s lab and to the members of Dr.
Riabowol’s lab: Arash, Subhash, Uma, Uyen, Yang and Ms. Donna for the ING3 (2A2)
antibody. Additionally, my gratitude goes to all members of the Translation lab at Tom Backer
Cancer Center, especially Mr. Brant Pohorelic for AQUA analysis and my best friend Alpana
Saxena. Thank you everyone for the friendship and generous support you have given me
throughout these years of my graduate study.
Moreover, I am deeply grateful and thankful to my family: my parents- Salma, and Ahmed;
my uncles Mohamed Naji Al-Amin, Mohamed Mohamed Al-Amin and Hamid Alwaly; my
brothers and sisters especially Mohamed Al-Husain and Zainab, for their unconditional love,
continuous care and constant support in every aspect of my life. Many thanks go, in particular, to
my husband, Abdullah, for his love and support, and also to my baby girl, Lama, for simply
being there.
I also must mention my indebtedness to my family members, friends and teachers in Canada
and back home in Saudi Arabia specifically Dr. Mohamed Basalamah from UQU and all
laboratory members at the Armed Forces Hospital, particularly Dr. Yousef Saleem. Last but not
least, I gratefully acknowledge financial support from the Ministry of Higher Education in the
Kingdom of Saudi Arabia and from the Royal Embassy of Saudi Arabia Cultural Bureau in
Canada.

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Dedication
To my family specially my mother Salma, brother Mohamed, husband Abdullah and my
daughters
Thank you for your love and support