REGULATORY ACTIONS OF LH AND FSH ON BREAST CANCER CELLS AND MAMMARY TUMORS IN RATS

SANCHEZ ANGEL MATIAS; FLAMINI MARINA INES; ZULLINO SARA; RUSSO ELEONORA; GIANNINI ANDREA; NACCARATO ANTONIO GIUSEPPE; GENAZZANI ANDREA RICCARDO; SIMONCINI TOMMASO

Frontiers in Endocrinology

Frontiers Media S.A.

Año: 2018

1664-2392

Gonadotrophins are mainly known to influence the body through the formation of gonadal steroids. However, receptors for luteinizing hormone (LHR) and follicular-stimulating hormone (FSHR) are present in a set of extra-gonadal tissues in humans and animals, but the functional relevance of these receptors is uncertain. In this manuscript we present experimental evidence that in T-47D breast cancer cells FSH and LH alter the expression of genes that are implicated in adhesion, motility ad invasion through activation of their receptors. Through miniarray technology we also found that LH influences the expression of a broad set of genes implicated in cancer biology in T-47D cells. Interestingly the regulatory actions of FSH and LH depend on the modality of exposure, with significant differences comparing pre-pubertal-like vs. post-menopausal-like amounts of gonadotrophins, as opposed to intermittent administration, such as during fertile life. Modulation of the circulating levels of gonadotrophins in an in vivo rat model of breast cancer progression was also studied, and a direct correlation was with the extent of cancer growth. These results support the hypothesis that gonadotrophins may have direct effects on extra-gonadal tissues. Plus, they highlight that they could potentially contribute to progression of breast cancer, particularly in post-menopausal women, where gonadotrophins? levels are higher. This research may ultimately lead to test the use of drugs that modulate gonadotrophins in breast cancer patients.