Triiodothyronine (T3) increases the expression of the amphiregulin (AREG) oncogene by activating extranuclear pathways in MCF-7 breast cancer cells
ABSTRACT Objective: Considering that the αvβ3 integrin plays an important role in tumor metastasis, this study investigated the involvement of these pathways in mediating the triiodothyronine (T3) effects on amphiregulin (AREG) expression. Materials and methods: We treated MCF-7 cells with T3 (10...
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Brazilian Society of Endocrinology and Metabolism
2025-01-01
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| Series: | Archives of Endocrinology and Metabolism |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S2359-39972024001000305&lng=en&tlng=en |
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| author | Maria Teresa De Sibio Fernanda Cristina Fontes Moretto Regiane Marques Castro Olimpio Miriane de Oliveira Lucas Solla Mathias Vinícius Vigliazzi Peghinelli Helena Paim Tilli Bianca Mariani Gonçalves Dariane Beatriz Marino Cardoso Larissa Silva Dall Aqua Igor de Carvalho Depra Mariana Menezes Lourenço Aline Carbonera Luvizon Paula de Oliveira Montandon Hokama Maria Tereza Nunes Marna Eliana Sakalem Célia Regina Nogueira |
| author_facet | Maria Teresa De Sibio Fernanda Cristina Fontes Moretto Regiane Marques Castro Olimpio Miriane de Oliveira Lucas Solla Mathias Vinícius Vigliazzi Peghinelli Helena Paim Tilli Bianca Mariani Gonçalves Dariane Beatriz Marino Cardoso Larissa Silva Dall Aqua Igor de Carvalho Depra Mariana Menezes Lourenço Aline Carbonera Luvizon Paula de Oliveira Montandon Hokama Maria Tereza Nunes Marna Eliana Sakalem Célia Regina Nogueira |
| author_sort | Maria Teresa De Sibio |
| collection | DOAJ |
| description | ABSTRACT Objective: Considering that the αvβ3 integrin plays an important role in tumor metastasis, this study investigated the involvement of these pathways in mediating the triiodothyronine (T3) effects on amphiregulin (AREG) expression. Materials and methods: We treated MCF-7 cells with T3 (10 nM) for 1 hour in the presence or absence of inhibitors for αvβ3 integrin (RGD peptide), MAPK (PD98059), PI3K (LY294002), and protein synthesis (cycloheximide [CHX]). A control group (C) received no T3 or inhibitors. Analyses of mRNA and protein expression were done using RT-qPCR and Western blot, respectively. Results: We observed that T3 increased AREG expression, an effect that was suppressed by all inhibitors. This finding indicates that the activation of the αvβ3 integrin signaling pathway, via PI3K, MAPK/ERK, is necessary for the T3-mediated effects on AREG expression and highlights the involvement of nongenomic mechanisms. In addition, CHX completely abolished T3-induced AREG mRNA expression, indicating that this effect requires prior protein synthesis. Conclusion: The identification that T3 acts through this signaling pathway holds considerable potential for clinical application, as it could lead to the development of specific drugs to block it. |
| format | Article |
| id | doaj-art-225890f24f9c4362a9db0797692378b9 |
| institution | Kabale University |
| issn | 2359-4292 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Brazilian Society of Endocrinology and Metabolism |
| record_format | Article |
| series | Archives of Endocrinology and Metabolism |
| spelling | doaj-art-225890f24f9c4362a9db0797692378b92025-01-21T07:45:27ZengBrazilian Society of Endocrinology and MetabolismArchives of Endocrinology and Metabolism2359-42922025-01-0168spe110.20945/2359-4292-2023-0094Triiodothyronine (T3) increases the expression of the amphiregulin (AREG) oncogene by activating extranuclear pathways in MCF-7 breast cancer cellsMaria Teresa De Sibiohttps://orcid.org/0000-0001-5674-3514Fernanda Cristina Fontes Morettohttps://orcid.org/0000-0003-3038-3068Regiane Marques Castro Olimpiohttps://orcid.org/0000-0002-4415-4744Miriane de Oliveirahttps://orcid.org/0000-0002-7003-667XLucas Solla Mathiashttps://orcid.org/0000-0002-1415-9536Vinícius Vigliazzi Peghinellihttps://orcid.org/0000-0002-4120-0880Helena Paim Tillihttps://orcid.org/0000-0002-8762-5999Bianca Mariani Gonçalveshttps://orcid.org/0000-0001-9054-9125Dariane Beatriz Marino Cardosohttps://orcid.org/0000-0002-8086-0347Larissa Silva Dall Aquahttps://orcid.org/0009-0009-4463-4025Igor de Carvalho Deprahttps://orcid.org/0000-0002-8093-8343Mariana Menezes Lourençohttps://orcid.org/0000-0002-1162-4404Aline Carbonera Luvizonhttps://orcid.org/0009-0008-8424-6441Paula de Oliveira Montandon Hokamahttps://orcid.org/0000-0003-3474-4422Maria Tereza Nuneshttps://orcid.org/0000-0003-3375-4020Marna Eliana Sakalemhttps://orcid.org/0000-0002-3143-4093Célia Regina Nogueirahttps://orcid.org/0000-0002-4014-0660ABSTRACT Objective: Considering that the αvβ3 integrin plays an important role in tumor metastasis, this study investigated the involvement of these pathways in mediating the triiodothyronine (T3) effects on amphiregulin (AREG) expression. Materials and methods: We treated MCF-7 cells with T3 (10 nM) for 1 hour in the presence or absence of inhibitors for αvβ3 integrin (RGD peptide), MAPK (PD98059), PI3K (LY294002), and protein synthesis (cycloheximide [CHX]). A control group (C) received no T3 or inhibitors. Analyses of mRNA and protein expression were done using RT-qPCR and Western blot, respectively. Results: We observed that T3 increased AREG expression, an effect that was suppressed by all inhibitors. This finding indicates that the activation of the αvβ3 integrin signaling pathway, via PI3K, MAPK/ERK, is necessary for the T3-mediated effects on AREG expression and highlights the involvement of nongenomic mechanisms. In addition, CHX completely abolished T3-induced AREG mRNA expression, indicating that this effect requires prior protein synthesis. Conclusion: The identification that T3 acts through this signaling pathway holds considerable potential for clinical application, as it could lead to the development of specific drugs to block it.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S2359-39972024001000305&lng=en&tlng=enTriiodothyroninebreast adenocarcinomaMCF-7 cellsAREGαvβ3 integrin |
| spellingShingle | Maria Teresa De Sibio Fernanda Cristina Fontes Moretto Regiane Marques Castro Olimpio Miriane de Oliveira Lucas Solla Mathias Vinícius Vigliazzi Peghinelli Helena Paim Tilli Bianca Mariani Gonçalves Dariane Beatriz Marino Cardoso Larissa Silva Dall Aqua Igor de Carvalho Depra Mariana Menezes Lourenço Aline Carbonera Luvizon Paula de Oliveira Montandon Hokama Maria Tereza Nunes Marna Eliana Sakalem Célia Regina Nogueira Triiodothyronine (T3) increases the expression of the amphiregulin (AREG) oncogene by activating extranuclear pathways in MCF-7 breast cancer cells Archives of Endocrinology and Metabolism Triiodothyronine breast adenocarcinoma MCF-7 cells AREG αvβ3 integrin |
| title | Triiodothyronine (T3) increases the expression of the amphiregulin (AREG) oncogene by activating extranuclear pathways in MCF-7 breast cancer cells |
| title_full | Triiodothyronine (T3) increases the expression of the amphiregulin (AREG) oncogene by activating extranuclear pathways in MCF-7 breast cancer cells |
| title_fullStr | Triiodothyronine (T3) increases the expression of the amphiregulin (AREG) oncogene by activating extranuclear pathways in MCF-7 breast cancer cells |
| title_full_unstemmed | Triiodothyronine (T3) increases the expression of the amphiregulin (AREG) oncogene by activating extranuclear pathways in MCF-7 breast cancer cells |
| title_short | Triiodothyronine (T3) increases the expression of the amphiregulin (AREG) oncogene by activating extranuclear pathways in MCF-7 breast cancer cells |
| title_sort | triiodothyronine t3 increases the expression of the amphiregulin areg oncogene by activating extranuclear pathways in mcf 7 breast cancer cells |
| topic | Triiodothyronine breast adenocarcinoma MCF-7 cells AREG αvβ3 integrin |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S2359-39972024001000305&lng=en&tlng=en |
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