Acetylcholine, Another Factor in Breast Cancer
Acetylcholine (ACh) is a neurotransmitter that regulates multiple functions in the nervous system, and emerging evidence indicates that it could play a role in cancer progression. However, this function is controversial. Previously, we showed that organophosphorus pesticides decreased the levels of...
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| Format: | Article |
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MDPI AG
2023-11-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/12/11/1418 |
| _version_ | 1797460120876089344 |
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| author | Juan P. Muñoz Gloria M. Calaf |
| author_facet | Juan P. Muñoz Gloria M. Calaf |
| author_sort | Juan P. Muñoz |
| collection | DOAJ |
| description | Acetylcholine (ACh) is a neurotransmitter that regulates multiple functions in the nervous system, and emerging evidence indicates that it could play a role in cancer progression. However, this function is controversial. Previously, we showed that organophosphorus pesticides decreased the levels of the enzyme acetylcholinesterase in vivo, increasing ACh serum levels and the formation of tumors in the mammary glands of rats. Furthermore, we showed that ACh exposure in breast cancer cell lines induced overexpression of estrogen receptor alpha (ERα), a key protein described as the master regulator in breast cancer. Therefore, here, we hypothesize that ACh alters the ERα activity through a ligand-independent mechanism. The results here reveal that the physiological concentration of ACh leads to the release of Ca<sup>+2</sup> and the activity of MAPK/ERK and PI3K/Akt pathways. These changes are associated with an induction of p-ERα and its recruitment to the nucleus. However, ACh fails to induce overexpression of estrogen-responsive genes, suggesting a different activation mechanism than that of 17ß-estradiol. Finally, ACh promotes the viability of breast cancer cell lines in an ERα-dependent manner and induces the overexpression of some EMT markers. In summary, our results show that ACh promotes breast cancer cell proliferation and ERα activity, possibly in a ligand-independent manner, suggesting its putative role in breast cancer progression. |
| first_indexed | 2024-03-09T17:00:37Z |
| format | Article |
| id | doaj.art-6da76c9fb5f04426bb720d45bd562df2 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-09T17:00:37Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-6da76c9fb5f04426bb720d45bd562df22023-11-24T14:30:21ZengMDPI AGBiology2079-77372023-11-011211141810.3390/biology12111418Acetylcholine, Another Factor in Breast CancerJuan P. Muñoz0Gloria M. Calaf1Laboratorio de Bioquímica, Departamento de Química, Facultad de Ciencias, Universidad de Tarapacá, Arica 1000007, ChileInstituto de Alta Investigación, Universidad de Tarapacá, Arica 1000000, ChileAcetylcholine (ACh) is a neurotransmitter that regulates multiple functions in the nervous system, and emerging evidence indicates that it could play a role in cancer progression. However, this function is controversial. Previously, we showed that organophosphorus pesticides decreased the levels of the enzyme acetylcholinesterase in vivo, increasing ACh serum levels and the formation of tumors in the mammary glands of rats. Furthermore, we showed that ACh exposure in breast cancer cell lines induced overexpression of estrogen receptor alpha (ERα), a key protein described as the master regulator in breast cancer. Therefore, here, we hypothesize that ACh alters the ERα activity through a ligand-independent mechanism. The results here reveal that the physiological concentration of ACh leads to the release of Ca<sup>+2</sup> and the activity of MAPK/ERK and PI3K/Akt pathways. These changes are associated with an induction of p-ERα and its recruitment to the nucleus. However, ACh fails to induce overexpression of estrogen-responsive genes, suggesting a different activation mechanism than that of 17ß-estradiol. Finally, ACh promotes the viability of breast cancer cell lines in an ERα-dependent manner and induces the overexpression of some EMT markers. In summary, our results show that ACh promotes breast cancer cell proliferation and ERα activity, possibly in a ligand-independent manner, suggesting its putative role in breast cancer progression.https://www.mdpi.com/2079-7737/12/11/1418acetylcholineestrogensestrogen receptor alphamuscarinic receptorbreast cancer |
| spellingShingle | Juan P. Muñoz Gloria M. Calaf Acetylcholine, Another Factor in Breast Cancer Biology acetylcholine estrogens estrogen receptor alpha muscarinic receptor breast cancer |
| title | Acetylcholine, Another Factor in Breast Cancer |
| title_full | Acetylcholine, Another Factor in Breast Cancer |
| title_fullStr | Acetylcholine, Another Factor in Breast Cancer |
| title_full_unstemmed | Acetylcholine, Another Factor in Breast Cancer |
| title_short | Acetylcholine, Another Factor in Breast Cancer |
| title_sort | acetylcholine another factor in breast cancer |
| topic | acetylcholine estrogens estrogen receptor alpha muscarinic receptor breast cancer |
| url | https://www.mdpi.com/2079-7737/12/11/1418 |
| work_keys_str_mv | AT juanpmunoz acetylcholineanotherfactorinbreastcancer AT gloriamcalaf acetylcholineanotherfactorinbreastcancer |