Follicle-stimulating hormone stimulates the tumourigenic behavior of breast cancer cells in vitro. (#203)
Breast cancer is the most commonly diagnosed cancer in women with one in nine Australian women diagnosed before the age of 85. Many of the known risk factors for developing breast cancer are associated with increased life time exposure to hormones, predominantly oestrogens. Follicle-stimulating hormone (FSH) may also have a role in breast cancer. FSH is frequently used in artificial reproductive technologies to stimulate folliculogenesis and oocyte development, and several epidemiological studies have reported an elevated breast cancer risk in some women who have undergone in vitro fertilization . Furthermore, elevated levels of serum FSH have been correlated with a more aggressive breast tumour phenotype in pre-menopausal women . Here, we report the expression of the FSH receptor (FSHR) and the in vitro tumourigenic effects of FSH at numerous concentrations. Using Real Time RT-PCR and Western immunoblotting we report the expression of FSHR in clinical breast cancers and oestrogen-receptor negative (ER-) and positive (ER+) breast cancer and fibroblastic breast disease cell lines and also a dose-dependent regulation of FSHR in response to FSH. Using a Real Time Cell Analyser (Roche Applied Science) we demonstrate that FSH stimulates the migration of both ER- breast cancer cells and cells derived from fibroblastic breast disease and also the invasion of ER- breast cancer cells. Finally, for the first time, we demonstrate that FSH stimulates the expression and activity of matrix metalloproteinases 2 and 9, ECM-degrading proteases that are strongly associated with tumour invasion and metastasis of breast cancer. This study provides novel evidence for a role for FSH in the progression and development of breast cancer. Although further studies are required, these findings may indicate that the use of FSH for the treatment of infertility could stimulate the tumourigenic activity of pre-existing breast cancer and fibroblastic breast cells.
- Pappo et al. 2008; The possible association between IVF and breast cancer incidence. Ann Surg Oncol. 15(4):1048-55.
- Hernandez et al. 2005; Circulating hormone levels in breast cancer patients. Correlation with serum tumor markers and the clinical and biological features of the tumors. Anticancer Research 25: 451-454.