Effects of TR-Beta Specific Agonists on Breast Cancer

Presenter's Name(s)

Lauren Mary CozzensFollow

Conference Year

January 2020

Abstract

Breast cancer is the most commonly diagnosed cancer in women worldwide, and the second most cause of cancer death in the United States. Survivors of breast cancer are more likely to be diagnosed with a second cancer, most frequently thyroid cancer. Notably, thyroid hormone receptor beta (TRb) may be an important link between thyroid and breast cancers as emerging evidence shows that loss of TRb is characteristic of breast and thyroid tumors. The presence of TRb, a nuclear receptor (NR) and likely tumor suppressor, has been associated with a good prognosis in BRCA-mutant breast cancer and responsivity to chemotherapy. This is in contrast to poorer outcomes observed with elevated levels of its isomer TRa. Thus, specific activation of TRb by thyroid hormone agonists holds great promise for the treatment of breast and thyroid cancers, yet data on the manipulation of TRb is limited. The purpose of this project was to determine the impacts of the TRb agonist, GC-1, on the phenotypic and growth characteristics of breast cancer cell lines. We hypothesized that TRb represents a novel NR target for which selective activation with isomer specific agonists may present alternative therapeutic interventions alone or as adjuvant therapy for treatment-resistant diseases.

Primary Faculty Mentor Name

Frances E. Carr, Ph D.

Graduate Student Mentors

Eric Bolf, Cole Davidson, Noelle Gillis

Faculty/Staff Collaborators

Frances Carr, Ph.D. (PI), Jennifer Tomczak (Collaborating Mentor), Eric Bolf (Graduate Student Mentor), Cole Davidson (Graduate Student Mentor), Noelle Gillis (Graduate Student Mentor)

Status

Undergraduate

Student College

College of Agriculture and Life Sciences

Program/Major

Molecular Genetics

Primary Research Category

Arts & Humanities

Abstract only.

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Effects of TR-Beta Specific Agonists on Breast Cancer

Breast cancer is the most commonly diagnosed cancer in women worldwide, and the second most cause of cancer death in the United States. Survivors of breast cancer are more likely to be diagnosed with a second cancer, most frequently thyroid cancer. Notably, thyroid hormone receptor beta (TRb) may be an important link between thyroid and breast cancers as emerging evidence shows that loss of TRb is characteristic of breast and thyroid tumors. The presence of TRb, a nuclear receptor (NR) and likely tumor suppressor, has been associated with a good prognosis in BRCA-mutant breast cancer and responsivity to chemotherapy. This is in contrast to poorer outcomes observed with elevated levels of its isomer TRa. Thus, specific activation of TRb by thyroid hormone agonists holds great promise for the treatment of breast and thyroid cancers, yet data on the manipulation of TRb is limited. The purpose of this project was to determine the impacts of the TRb agonist, GC-1, on the phenotypic and growth characteristics of breast cancer cell lines. We hypothesized that TRb represents a novel NR target for which selective activation with isomer specific agonists may present alternative therapeutic interventions alone or as adjuvant therapy for treatment-resistant diseases.