Regulatory Actions of LH and Follicle-Stimulating Hormone on Breast Cancer Cells and Mammary Tumors in Rats
Authors: Antonio Giuseppe Naccarato
Paolo Mannella
Marina Ines Flamini
Eleonora Russo
Sara Zullino
Andrea Riccardo Genazzani
Andrea Giannini
Tommaso Simoncini
Angel Matias Sanchez
Journal: Frontiers in Endocrinology (2018)
Discipline: CLINICAL MEDICINE
Keywords: LH; breast cancer; cell motility; follicle stimulating hormone; moesin and focal adhesion kinase.
Affiliations: Molecular and Cellular Gynecological Endocrinology Laboratory (MCGEL), Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy., Laboratorio de Transducción de Señales y Movimiento Celular, Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Mendoza, Argentina., Laboratorio de Biología Tumoral, Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Mendoza, Argentina., Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy.

Abstract:  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. 

Retracted: No

PubPeer comments:
 Figure 4C and 4E appear to have some images which overlap. There are other papers with image concerns with overlapping authors https: pubpeer.com search?q=Sanchez+flamini *** ![file] , 
 Thank you very much for reminding us of the repetition. I checked the original data and reports. Indeed, it is a mistake during figure preparation. Surely, I will ask the journal for the correction soon. Thank you very much for your efforts in making the scientific publication solid and clean. Best Regards, Matias ,