Androgen Receptor Activation Induces Senescence in Thyroid Cancer Cells
Thyroid cancer (TC) is the most common endocrine malignancy, with an approximately three-fold higher incidence in women. TCGA data indicate that androgen receptor (AR) RNA is significantly downregulated in PTC. In this study, AR-expressing 8505C (anaplastic TC) (84E7) and K1 (papillary TC) cells experienced an 80% decrease in proliferation over 6 days of exposure to physiological levels of 5α-dihydrotestosterone (DHT). In 84E7, continuous AR activation resulted in G1 growth arrest, accompanied by a flattened, vacuolized cell morphology, with enlargement of the cell and the nuclear area, which is indicative of senescence; this was substantiated by an increase in senescence-associated β-galactosidase activity, total RNA and protein content, and reactive oxygen species. Additionally, the expression of tumor suppressor proteins p16, p21, and p27 was significantly increased. A non-inflammatory senescence-associated secretory profile was induced, significantly decreasing inflammatory cytokines and chemokines such as IL-6, IL-8, TNF, RANTES, and MCP-1; this is consistent with the lower incidence of thyroid inflammation and cancer in men. Migration increased six-fold, which is consistent with the clinical observation of increased lymph node metastasis in men. Proteolytic invasion potential was not significantly altered, which is consistent with unchanged MMP/TIMP expression. Our studies provide evidence that the induction of senescence is a novel function of AR activation in thyroid cancer cells, and may underlie the protective role of AR activation in the decreased incidence of TC in men.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Cancers - 15(2023), 8 vom: 07. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gupta, Anvita [VerfasserIn] |
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| Links: |
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| Themen: |
Androgen receptor |
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| Anmerkungen: |
Date Revised 19.05.2023 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3390/cancers15082198 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM356927784 |
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| 520 | |a Thyroid cancer (TC) is the most common endocrine malignancy, with an approximately three-fold higher incidence in women. TCGA data indicate that androgen receptor (AR) RNA is significantly downregulated in PTC. In this study, AR-expressing 8505C (anaplastic TC) (84E7) and K1 (papillary TC) cells experienced an 80% decrease in proliferation over 6 days of exposure to physiological levels of 5α-dihydrotestosterone (DHT). In 84E7, continuous AR activation resulted in G1 growth arrest, accompanied by a flattened, vacuolized cell morphology, with enlargement of the cell and the nuclear area, which is indicative of senescence; this was substantiated by an increase in senescence-associated β-galactosidase activity, total RNA and protein content, and reactive oxygen species. Additionally, the expression of tumor suppressor proteins p16, p21, and p27 was significantly increased. A non-inflammatory senescence-associated secretory profile was induced, significantly decreasing inflammatory cytokines and chemokines such as IL-6, IL-8, TNF, RANTES, and MCP-1; this is consistent with the lower incidence of thyroid inflammation and cancer in men. Migration increased six-fold, which is consistent with the clinical observation of increased lymph node metastasis in men. Proteolytic invasion potential was not significantly altered, which is consistent with unchanged MMP/TIMP expression. Our studies provide evidence that the induction of senescence is a novel function of AR activation in thyroid cancer cells, and may underlie the protective role of AR activation in the decreased incidence of TC in men | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a DHT | |
| 650 | 4 | |a androgen receptor | |
| 650 | 4 | |a senescence | |
| 650 | 4 | |a thyroid cancer | |
| 650 | 4 | |a tumor migration/invasion | |
| 700 | 1 | |a Carnazza, Michelle |e verfasserin |4 aut | |
| 700 | 1 | |a Jones, Melanie |e verfasserin |4 aut | |
| 700 | 1 | |a Darzynkiewicz, Zbigniew |e verfasserin |4 aut | |
| 700 | 1 | |a Halicka, Dorota |e verfasserin |4 aut | |
| 700 | 1 | |a O'Connell, Timmy |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Dadafarin, Sina |e verfasserin |4 aut | |
| 700 | 1 | |a Shin, Edward |e verfasserin |4 aut | |
| 700 | 1 | |a Schwarcz, Monica D |e verfasserin |4 aut | |
| 700 | 1 | |a Moscatello, Augustine |e verfasserin |4 aut | |
| 700 | 1 | |a Tiwari, Raj K |e verfasserin |4 aut | |
| 700 | 1 | |a Geliebter, Jan |e verfasserin |4 aut | |
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