Probing the Role of High Mobility Group A1 (hmga1) in Chemoresistance Using 5-Fluorodeoxyuridine
College
College of Arts and Sciences
Department
Chemistry, Physics, Geology, & the Environment
Faculty Mentor
Takita Sumter, Ph.D.
Abstract
Chemoresistance is a major limitation to effective cancer treatment regimens. Specifically, cancer stem cells, self-renewing cells that can differentiate, provide a pathway to escape treatments by targeting rapid cell division pathways. High mobility group A1 (hmga1) is implicated in the initiation and progression of various cancers and may be involved in the genetic events leading to the growth of cancer stem cells. Mice bearing the (hmga1 transgene develop aggressive lymphoid malignancies and are less responsive to chemotherapies that have been tested. To this end, we explored the role of (hmga1 in chemoresistance using 5-fluorodeoxyuridine (5-FdUrd). 5-FdUrd is the active antimetabolite of a mainstay in cancer treatment whose activity is based on the misincorporation of fluoropyrimidines into DNA and RNA during their synthesis. Studies were conducted using HCT-116 colorectal cancer cells with high endogenous levels of hmga1 proteins. These cells were treated with varying concentrations of 5-FdUrd and IC50 values were determined to be comparable to, but slightly higher than, previously published values. Silencing of (hmga1 expression by siRNA duplexes targeting different genetic regions enhanced sensitivity to 5-FdUrd by greater than 1.5- to 3-fold when compared to native HCT-116 cells. Collectively, we provide data that support the role of (hmga1 in orchestrating the ability of cancer cells to evade the impacts of chemotherapy, particularly those targeting cell division pathways. We expect that this work will contribute to an expanded understanding of cancer initiation and progression and will facilitate development of more effective cancer therapies.
Recognized with an Award?
1st place, Life Science Oral Presentations, SAEOPP McNair/SSS Scholars Research Conference, June 2017
Previously Presented/Performed?
SAEOPP McNair/SSS Scholars Research Conference, Atlanta, Georgia, June 2017
Grant Support?
Supported by a Ronald E. McNair Post-Baccalaureate Achievement Program grant from the U.S. Department of Education and by an SC INBRE grant from the National Institute of General Medical Sciences (NIH-NIGMS)
Start Date
20-4-2018 3:30 PM
Probing the Role of High Mobility Group A1 (hmga1) in Chemoresistance Using 5-Fluorodeoxyuridine
West 219
Chemoresistance is a major limitation to effective cancer treatment regimens. Specifically, cancer stem cells, self-renewing cells that can differentiate, provide a pathway to escape treatments by targeting rapid cell division pathways. High mobility group A1 (hmga1) is implicated in the initiation and progression of various cancers and may be involved in the genetic events leading to the growth of cancer stem cells. Mice bearing the (hmga1 transgene develop aggressive lymphoid malignancies and are less responsive to chemotherapies that have been tested. To this end, we explored the role of (hmga1 in chemoresistance using 5-fluorodeoxyuridine (5-FdUrd). 5-FdUrd is the active antimetabolite of a mainstay in cancer treatment whose activity is based on the misincorporation of fluoropyrimidines into DNA and RNA during their synthesis. Studies were conducted using HCT-116 colorectal cancer cells with high endogenous levels of hmga1 proteins. These cells were treated with varying concentrations of 5-FdUrd and IC50 values were determined to be comparable to, but slightly higher than, previously published values. Silencing of (hmga1 expression by siRNA duplexes targeting different genetic regions enhanced sensitivity to 5-FdUrd by greater than 1.5- to 3-fold when compared to native HCT-116 cells. Collectively, we provide data that support the role of (hmga1 in orchestrating the ability of cancer cells to evade the impacts of chemotherapy, particularly those targeting cell division pathways. We expect that this work will contribute to an expanded understanding of cancer initiation and progression and will facilitate development of more effective cancer therapies.
