Keywords
Cancer; Twist1; Motility; Estradiol; MCF-7; Tamoxifen
Abstract
Breast cancer is a highly malignant cancer and is known to be grouped into three main types: adenocarcinoma, invasive ductal carcinoma (IDC) and ductal carcinoma. Breast cancer commonly arises as adenocarcinoma, located in the milk ducts, and becomes IDC when it spreads into the surrounding tissue from the influence of cytokines and hormones. This study outlines the rate of proliferation and motility of a type of adenocarcinoma, MCF-7-TamR, to become invasive ductal carcinoma when Twist1 is downregulated and exposed to TGF- and estradiol (E2) in-vitro. We hypothesize that the downregulation of Twist1 will reduce cell adhesion and cytoskeleton proteins to prevent tumor movement and proliferation when exposed to tumor promoters in-vitro. For the proliferation study, cells were analyzed for variation in morphology, cell density, and HER2/COX2 expression over a 2-day to 7-day period when exposed to 10nM TGF- and 0.1nM, 10nM, or 10 of E2 in the presence or knockdown of Twist1. After imaging with a bright-field microscope with phase contrast and RT-qPCR, Twist1 knockdown had a significant effect of reducing apoptosis post prolonged exposure of E2 and TGF- . For the motility study, cells were exposed 10nM TGF- and 0.1nM, 10nM, or 10 of E2 with either Twist1 presence or knockdown. The exposure of E2 showed a biphasic effect by increasing early motility, 24hr, but reducing later motility, 48hr, by primary utilizing actin-based motility. TGF- reverses this trend by decreasing early motility but increasing later motility independent of E2 by utilizing microtubule-based motility. The knockdown of Twist1 prevents TGF- effects of increasing later motility and restores MCF-7 cells sensitivity to E2. Significant difference between different treatment groups were found in both proliferation and motility studies. These finding help to indicate that TGF- and Twist1 has effect on hormonal breast cancer in increasing the likelihood of MCF-7 adenocarcinoma becoming IDC in-vitro, but need be further investigated to assess likelihood in-vivo.
Thesis Completion Year
2025
Thesis Completion Semester
Spring
Thesis Chair
Borgon, Robert
College
College of Medicine
Department
Burnett School of Biomedical Sciences
Thesis Discipline
Molecular Biology
Language
English
Access Status
Open Access
Length of Campus Access
None
Campus Location
Orlando (Main) Campus
STARS Citation
Scott, Thomas L. III, "Impact of TGF-β and Twist1 on Motility and Proliferation in Estradiol-Treated MCF-7 TamR cells in-vitro" (2025). Honors Undergraduate Theses. 251.
https://stars.library.ucf.edu/hut2024/251