The role of FOX Genes on Chromosome 6 on Breast Cancer

• Author / Creator

  Fahed Elian

• The transcription factors FOXC1, FOXQ1, and FOXF2 (FOX cluster on chromosome 6) are members of the forkhead family that play a role in a plethora of biological processes during development and tumorigenesis. Emerging studies in the last decade have suggested a role of the FOX cluster in breast cancer (BC). The majority of the research however has focused on one subtype of BC known as basal/triple negative breast cancer. Very limited studies have investigated the role of the FOX cluster in other BC subtypes such as luminal and HER2 subtypes. Thus, studies that examine the role of the FOX cluster in other subtypes of BC are needed.
  In this thesis, I examined the expression, copy numbers, and mutations of the FOX cluster genes across BC subtypes in BC patient samples and cell lines. I revealed for the first time that FOXQ1 expression varied across breast cancer subtypes and most importantly that low expression of FOXQ1 is associated with poor prognosis in BC patients. Moreover, I showed that FOXC1 expression also varied across BC subtypes and that the protein of FOXC1 is more stable in basal/TNBC cell lines. I also showed that the FOX cluster genes had copy number variation in BC subtypes, however I showed that their mRNA expression is independent from copy number variations. Finally, I found three novel mutations of FOXC1 in 3 different BC patients that were predicted to be likely-pathogenic, and that FOXC1 expression is significantly positively correlated with FOXF2 expression in BC patients.
  My findings suggest dual roles of the FOX cluster in BC in different BC subtypes. Based upon my research I suggest that the FOX cluster acts more like “onco-genes” in basal BC, but a “tumor-suppressor genes” in HER2 and luminal BC subtype

• Subjects / Keywords

  • Breast cancer
  • transcription factors
  • prognostic markers
  • mRNA
  • gene copy number

• Graduation date

  Spring 2021

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-zc8m-kn29

• 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.