title: Effect of androgens on different breast cancer cells co-cultured with or without breast adipose fibroblasts.
abstract: About 70% of breast tumors express androgen receptors. In addition, there is clinical evidence suggesting that androgens can inhibit mammary epithelial proliferation. Vice versa, there is also significant evidence indicating that androgens can increase the risk of breast cancer via multiple mechanisms, e.g. direct conversion to estrogens that can bind to the estrogen receptor and thereby stimulate cell proliferation. We examined the effect of testosterone (T) and dihydroxytestosterone (DHT) on cell proliferation, pS2 and Ki-67 expression in three different breast cancer cell lines alone or in co-culture with primary human breast adipose fibroblasts (BAFs) obtained from breast cancer patients. In the co-cultures, T induced cell proliferation, pS2 and Ki-67 expression in the estrogen receptor positive (ER(+)) MCF-7 and T47D cells. This was not observed in the (ER(-)) MDA-MB-231 cells. The differences might be explained by the high expression of aromatase, which converts androgens to estrogens in BAFs followed by ER-mediated cell proliferation. In line with this absence of increased cell proliferation, pS2 and Ki-67 expression was observed in the presence of DHT, which is not a substrate for aromatase. In contrast, DHT caused a significant suppression of cell proliferation (68% and 38%), pS2 and Ki-67 expression in the (ER(+)) MCF-7 and T47D cells. More importantly, DHT decreased cell proliferation in (ER(-)) MDA-MB-231 cells by 38%. The results suggest that androgens that cannot be aromatized, like DHT, may provide a perspective for treatment of breast cancer patients, especially those with triple negative breast cancer.
authors.affiliation: Division of Environmental Toxicology, Chulabhorn Graduate Institute, Bangkok, Thailand; Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok, Thailand; Center of Excellence on Environmental Health, Toxicology and management of Chemicals, Bangkok, Thailand; Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands; Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Thailand. Electronic address: suthat.c@bidi.mail.go.th.
authors.forename: Suthat
authors.initials: S
authors.lastname: Chottanapund
authors.forename: Majorie B M
authors.initials: MB
authors.lastname: Van Duursen
authors.forename: Panida
authors.initials: P
authors.lastname: Navasumrit
authors.forename: Potchanee
authors.initials: P
authors.lastname: Hunsonti
authors.forename: Supatchaya
authors.initials: S
authors.lastname: Timtavorn
authors.forename: Mathuros
authors.initials: M
authors.lastname: Ruchirawat
authors.forename: Martin
authors.initials: M
authors.lastname: Van den Berg
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods*; D004958:Estradiol / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D006915:Hydroxytestosterones / Q000378:metabolism / Q000494:pharmacology; D042361:Mammary Glands, Human / Q000166:cytology*; D011960:Receptors, Estrogen / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000728:Androgens; D006915:Hydroxytestosterones; D011960:Receptors, Estrogen; D013739:Testosterone; D004958:Estradiol
keywords: Androgens; Aromatase; Breast adipose fibroblasts; Breast tumor cells; Cell proliferation; Co-culture; Estrogen receptor; Ki-67; pS2