Date of Graduation
5-2024
Document Type
Thesis
Degree Name
Bachelor of Science in Biology
Degree Level
Undergraduate
Department
Biological Sciences
Advisor/Mentor
Bailey, Tameka
Committee Member
Du, Yuchun
Second Committee Member
Chapman, Kate
Third Committee Member
Roddy, James
Abstract
Introduction: Brain metastases is one of the leading causes of breast cancer mortality and rates continue to increase. It has been previously shown that cholesterol metabolism is an important regulator of cancer progression. 24(S)-hydroxycholesterol (24-HC) and 27- hydroxycholesterol (27-HC) are cholesterol derivatives primarily found in the brain but their role in regulating oncoprotein expression remains unclear. The goal of this thesis was to determine the effect of 24-HC and 27-HC on in-vitro metastatic phenotypes of breast cancer cells previously shown by the Bailey laboratory to metastasize to the brain in a hematogenous metastasis xenograft model.
Materials and Methods: Western blot and fluorescence microscopy were used to assess the 24- HC and 27-HC dependent expression of the epidermal growth factor receptor (EGFR) and aurora kinase A (AURKA) in breast cancer cells which have the propensity to metastasize to the brain. EGFR and AURKA are two oncoproteins previously shown by the Bailey laboratory and others to be upregulated in breast cancer cells that metastasize to the brain (Simeon et al., 2021 and unpublished data). The anchorage independent growth assay, tubule formation assay and cell migration assay were used to assess the in-vitro phenotypes of brain metastatic breast cancer cells treated with 24-HC and 27-HC.
Results: Expression of EGFR and AURKA by hydroxycholesterols is suppressed in the highly brain metastatic cell line, MDA-MB-231 ANGPTL4-mGFP, but is induced in the MDA-MB-231 mGFP cell line. 24-HC and 27-HC suppressed anchorage independent growth and tubule formation in MDA-MB-231 ANGPTL4-mGFP cell line. However, the hydroxycholesterols promoted cellular migration in MDA-MB-231 ANGPTL4-mGFP cell line.
Conclusion: 24-HC and 27-HC are pleotropic modulators of the in vitro metastatic phenotypes of breast cancer cells.
Keywords
cholesterol metabolism; cancer treatment
Citation
Iroabuchi, C. (2024). The Impact of Brain Cholesterol (24-hydroxycholesterol (24-HC) and 27- hydroxycholesterol (27-HC)) on Invitro Phenotypes of Brain Metastatic Breast Cancer Cells. Biological Sciences Undergraduate Honors Theses Retrieved from https://scholarworks.uark.edu/biscuht/115
