Document Type

Thesis

Date of Award

8-2022

School/College

College of Science, Engineering, and Technology (COSET)

Degree Name

MS in Biology

Committee Chairperson

: Audrey Player

Committee Member 1

Erica Cassimere

Committee Member 2

Marian Hillar

Committee Member 3

Jahmario Williams

Keywords

Breast Cancer, KIF18B, MYBL1, MYBL2, TCF19, Triple Negative Breast Cancer

Abstract

The aggressive behavior in triple-negative breast cancer (TNBC) is due to genetic signaling events, which call for the comprehensive analyses of genes differentially regulated in the cancers. Our laboratory previously found that MYBL1 was over-expressed in a fraction of the TNBC, compared to some luminal, and other breast cancer subtypes. The MYBL1 gene is a proto-oncogene that serves as a strong transcriptional activator. The gene is involved in signaling events related to cell cycle signaling, differentiation, proliferation, and apoptosis, all which are differentially regulated in cancers. Because MYBL1 is a transcription regulator, involved in cancer-related mechanisms and differentially expressed in TNBC, our lab designed studies to better characterize the gene in TNBC. We performed shRNA lentiviral knockdown of MYBL1 in TNBC as the first goal to identify genes directly or indirectly affected by knockdown of the MYBL1 gene in these cancers. Our hypothesis is that some (not all) genes identified by this method likely cooperate with MYBL1 to affect the genotype and phenotype of TNBC. The TCF19 and KIF18b genes were two of the first candidate genes identified in our knockdown study. When MYBL1 was knocked down, TCF19 and KIF18b were also downregulated. Although we performed preliminary analyses of TCF19 and KIF18b RNA transcript levels in cell lines and using online patient datasets, a main goal of the current study was to examine TCF19 and KIF18b protein expression in clinically diagnosed TNBC (tissue) patient samples. We want to view, in situ, the protein level of our candidate genes in tissue samples isolated from women with clinically described breast cancer. Since TCF19 and KIF18b genes are downregulated when MYBL1 is knocked down, we will determine if these genes are co-expressed in the same tissue samples as MYBL1 protein. We also expand our bioinformatic analyses of the three genes, but the focus is protein analyses of MYBL1, TCF19 and KIF18b in patients’ tissues with defined clinical diagnoses.

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