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Thyroid hormones and their receptors in the regulation of cell proliferation
Monika Puzianowska-Kuznicka1, Maciej Pietrzak, Olga Turowska
1Department of Endocrinology, Medical Research Center, Polish Academy of Sciences, Warszawa, Poland. monika@amwaw.edu.pl
Abstract:
In the present work, we have reviewed data showing that triiodothyronine and its nuclear receptors modify expression of different genes/proteins involved in cell cycle control beginning from growth factors (such as EGF and TGF-beta), to cell surface receptors (EGFR), as well as proteins acting at the cell membrane (Ras), various transcription factors (c-Fos, c-Myc, E2F1), cyclins, Cip/Kip family of cdk2 inhibitors, and p53 inhibitor Mdm2 (Table 1). We have shown how TRs are also able to modify the fate of a cell, thanks to their ability to form complexes with other transcription factors such as p53 - a key regulator of apoptosis and proliferation. Available data show that the function of thyroid hormones and of their receptors on cell proliferation is not homogenous. In fact, it strongly depends on the cell type, its developmental state (progenitor or differentiated), its patho-physiological state (normal or tumor cell), and the so-called 'cellular context'. Therefore, it is not possible to uniformly recommend T3 treatment or T3 depletion to stop or initiate proliferation of all cell types. Instead, a very individual and careful action should be considered.
Insights
Thyroid hormones and their receptors (TRs) influence cell cycle genes, impacting cell fate. Their effect on cell proliferation varies greatly by cell type and context, requiring individualized treatment strategies.
Area of Science:
- Molecular Biology
- Cell Biology
- Endocrinology
Background:
- Thyroid hormones, particularly triiodothyronine (T3), play crucial roles in cellular processes.
- Nuclear receptors for thyroid hormones (TRs) are key regulators of gene expression.
- The precise impact of T3 and TRs on cell proliferation is complex and context-dependent.
Purpose of the Study:
- To review existing data on how T3 and TRs modulate genes and proteins involved in cell cycle control.
- To elucidate the role of TRs in regulating cell fate, including apoptosis and proliferation.
- To analyze the factors influencing the heterogeneous effects of thyroid hormones on cell proliferation.
Main Methods:
- Literature review of studies investigating the effects of triiodothyronine and its nuclear receptors on cell cycle regulators.
- Analysis of data on gene and protein expression changes induced by T3 and TRs.
- Examination of TR interactions with other transcription factors like p53.
Main Results:
- T3 and TRs modify the expression of numerous cell cycle-related genes and proteins, including growth factors, receptors, transcription factors (e.g., c-Fos, c-Myc, E2F1), cyclins, and inhibitors (e.g., Mdm2).
- TRs can form complexes with transcription factors such as p53, influencing apoptosis and proliferation.
- The effect of thyroid hormones on cell proliferation is highly variable, depending on cell type, developmental stage, and patho-physiological state.
Conclusions:
- Thyroid hormone action on cell proliferation is not uniform and is significantly influenced by cellular context.
- A one-size-fits-all approach to T3 treatment or depletion for controlling cell proliferation is not feasible.
- Careful, individualized strategies are necessary when considering thyroid hormone modulation for cell proliferation control.
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