Overlapping Actions of L-Thyroxine (T4) and Steroids in Breast Cancer Cells: Mediation by Cell Surface Integrin αvβ3

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Published Jan 6, 2024
DOI: https://doi.org/10.18103/mra.v11i12.4963

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Main Article Content

Aleck Hercbergs
Oncology, The Cleveland Clinic, Cleveland OH USA
Hung-Yun Lin
Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
Shaker A. Mousa
NanoPharmaceuticals LLC, Troy, NY USA
Matthew Leinung
Department of Medicine, Albany Medical College, Albany, NY USA
Paul J. Davis
NanoPharmaceuticals LLC, Troy, NY USA; Department of Medicine, Albany Medical College, Albany, NY USA

Abstract

The overlap of actions of nonpeptide small endocrine molecules—thyroid hormone and steroids—include two panels of actions. One set is initiated at the nuclear receptors for these hormones and a second set of actions for both hormones is initiated at the extracellular domain of plasma membrane integrin αvβ3. This brief review is concerned with integrin-based receptors on breast cancer cells. On such cells, thyroid hormone as L-thyroxine (T4) at physiological concentrations can stimulate proliferation of breast cancer cells via the thyroid hormone analogue receptor on αvβ3 and, in the absence of estrogen, via the nuclear estrogen receptor-α (ER α). Such observations emphasize the postmenopausal relevance of nuclear estrogen receptor. The deaminated T4 derivative, tetraiodothyroacetic acid (tetrac), blocks T4 actions at the integrin. An androgen receptor on the integrin mediates stimulation of breast cancer cell proliferation by dihydrotestosterone (DHT). T4 controls the activation state of the integrin, a factor that may determine the accessibility of the androgen receptor on αvβ3 to DHT and thus to DHT-driven cell proliferation. An estrogen receptor appears to be present on the integrin, but its functions have not been defined. It is not yet known whether tetrac alters function of the steroid receptors that are adjacent to the T4 binding site on αvβ3. The overlap of T4 and steroid functions in breast cancer cells may offer additional options for clinical management of this type of cancer.

Keywords: integrin αvβ3, L-thyroxine (T4), dihydrotestosterone (DHT), estrogen receptor-α (ER α),, breast cancer cell proliferation

Article Details

How to Cite
HERCBERGS, Aleck et al. Overlapping Actions of L-Thyroxine (T4) and Steroids in Breast Cancer Cells: Mediation by Cell Surface Integrin αvβ3. Medical Research Archives, [S.l.], v. 11, n. 12, jan. 2024. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/4963>. Date accessed: 26 dec. 2024. doi: https://doi.org/10.18103/mra.v11i12.4963.
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Issue
Vol 11 No 12 (2023): December Issue, Vol.11, Issue 12
Section
Research Articles

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