Regulatory actions of LH and follicle-stimulating hormone on breast cancer cells and mammary tumors in rats

Gonadotrophins are mainly known to influence the body through the formation of gonadal steroids. However, receptors for luteinizing hormone (LH) and follicular-stimulating hormone (FSH) are present in a set of extra-gonadal tissues in humans and animals, but their functional relevance is uncertain....

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Detalhes bibliográficos
Autores: Sanchez, Angel Matias, Flamini, Marina Ines, Zullino, Sara, Russo, Eleonora, Giannini, Andrea, Mannella, Paolo, Naccarato, Antonio Giuseppe, Genazzani, Andrea Ricardo, Simoncinii, Tommaso
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2018
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositório:CONICET Digital (CONICET)
Idioma:inglês
OAI Identifier:oai:ri.conicet.gov.ar:11336/90556
Acesso em linha:http://hdl.handle.net/11336/90556
Access Level:Acceso aberto
Palavra-chave:BREAST CANCER
CELL MOTILITY
FOLLICLE STIMULATING HORMONE
LH
MOESIN AND FOCAL ADHESION KINASE
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
Descrição
Resumo:Gonadotrophins are mainly known to influence the body through the formation of gonadal steroids. However, receptors for luteinizing hormone (LH) and follicular-stimulating hormone (FSH) are present in a set of extra-gonadal tissues in humans and animals, but their functional relevance is uncertain. In this article, we present experimental evidence that, in T-47D breast cancer (BC) cells, FSH, and LH alter the expression of genes involved in adhesion, motility, and invasion through the activation of their receptors. Using miniarray technology we also found that LH influences the expression of a broad set of genes involved in cancer biology in T-47D cells. Interestingly, the regulatory actions of FSH and LH depend on the modality of exposure, with significant differences between pre-pubertal-like vs. post-menopausal-like amounts of gonadotrophins, but not after intermittent administration, representative of fertile life. We also studied the modulation of the circulating levels of gonadotrophins in an in vivo rat model of BC progression and observed a direct correlation with the extent of cancer growth. These results support the hypothesis that gonadotrophins may have direct effects on extra-gonadal tissues. They also highlight that gonadotrophins could potentially contribute to BC progression, particularly in post-menopausal women who typically have higher gonadotrophin levels. This research may ultimately lead to testing the use of gonadotrophin-modulating drugs in BC patients.