Date of Award
College of Science, Engineering, and Technology (COSET)
MS in Biology
Committee Member 1
Committee Member 2
knock-down, Breast Cancer, MYBL1, Triple Negative
Triple Negative Breast Cancer (TNBC) is defined as negative for three genes, estrogen receptor (ESR), progesterone receptor (PR) and Human epidermal growth factor receptor (HER2-neu) genes. Previous data show the V-Myb Avian Myel oblast Viral Oncogene Homolog Like 1 (MYBL1) gene is over-expressed in Triple negative breast cancer cell line (MDA-MB231). MYBL1 belongs to the MYB family of genes which are transcription factors and proto-oncogenes which are associated with cell cycle regulation, apoptosis, and differentiation, all of which are key events associated with cancers. It could be that MYBL1 contributes to these same processes in TNBC. Instead of studying MYBL1’s contribution to several of these processes, we were mainly concerned with identifying genes that were either directly or indirectly affected by down-regulation of MYBL1 gene. Utilizing a gene silencing approach helps to identify genes that cooperate with MYBL1 in the signaling processes in cancer. Although the focus of our laboratory is TNBC, there are two parts to this current study, one that examines MYBL1 in luminal cancers cell line (MCF7) and one that examines MYBL1 in TNBC, designated Part 1 and Part 2, respectively. For Part 1, we performed analyses of MCF7 (Luminal breast cancer cell line) receptor positive cells where estrogen receptor gene was silenced; and another MCF7 preparation where cMYB gene was silenced. Both datasets were obtained from Gene Expression Omnibus (GEO). These datasets were chosen because even though they were neither TNBC or directly involved MYBL1 as the primary target, comparative analyses of both datasets showed MYBL1 knock-down (KD). We reasoned that even under these conditions, genes either directly or indirectly associated with MYBL1 might be identified. For Part 2 of this study, short hairpin RNA (shRNA) lentiviral transduction was used to down-regulate MYBL1 in MDA MB231 TNBC cells. A substantial number of reliable differentially expressed genes were identified here. Overall, genes recognized as associated with MYBL1 in the MCF7 luminal preparations (Part 1) were drastically different from genes identified as associated with MYBL1 in the TNBC KD study (Part 2). In both datasets, we identify novel genes that appear to be coordinately expressed with MYBL1 in breast cancers. This study led to identification of candidate genes that might be important towards the study of characterizing MYBL1 expression in TNBC. Two of these genes, transcription factor 19 (TCF19) and Kinesin-like protein (kinesin family member 18B) (KIF18B) have been experimentally validated. MYBL1 is a strong candidate gene to study for its contribution to the development of TNBC. Continued analyses of these genes and their relationship to MYBL1 should lead to a better understanding of signaling processes in breast cancers.
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Abdulrahman, Nabras Mahmoud, "V-Myb Avian Myel oblast Viral Oncogene Homolog Like 1 (MYBL1) Knockdown and its Role in a Triple Negative Breast Cancer" (2021). Theses (2016-Present). 18.