Interleukin-3: a putative protective factor against breast cancer which is secreted by male but not female breast fibroblasts.
The enzyme 17 beta-hydroxysteroid dehydrogenase (17-HSD) is a key regulator of intracellular 17 beta-estradiol (E2), which is associated with breast cancer and is influenced by paracrine factors released by breast-cancer fibroblasts. Since the incidence of breast cancer is much higher in females than in males, we have used an in vitro cell culture system to investigate whether male fibroblasts may inhibit breast-cancer genesis by restricting the intracellular accumulation of E2. Fibroblasts were obtained from normal males and females undergoing reduction mammoplasty, and from females with benign or malignant breast lesions. Fibroblast-conditioned medium (CM) was incubated with the established breast-cancer cell line, MCF-7, and its effects on 17-HSD activity were assessed. CM (25% v/v) from male breast fibroblasts had a significant inhibitory effect on reductive 17-HSD, decreasing E2 production. This was in direct contrast to the effects of CM from female breast fibroblasts, which had a powerful stimulatory effect on reductive 17-HSD. RT-PCR allowing simultaneous detection of a range of cytokines was performed on each type of fibroblast. IL-3 mRNA was consistently detected in fibroblasts from male but not female breast tissue. Addition of rhIL-3 to cultures of MCF-7 caused a reduction in 17-HSD activity and addition of a polyclonal antibody directed against IL-3 to male CM completely reversed the inhibitory effects of CM. Thus, male breast fibroblasts may be responsible for secreting IL-3-like factors which, given the considerably lower incidence rates of breast cancer in men, may have a protective effect against breast cancer.
Speirs
V
V
Department of Medicine, University of Hull, UK.
Birch
M A
MA
Boyle-Walsh
E
E
Green
A R
AR
Gallagher
J A
JA
White
M C
MC
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D001940:Breast / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D001943:Breast Neoplasms / Q000517:prevention & control*; D018567:Breast Neoplasms, Male / Q000517:prevention & control*; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000096:biosynthesis*; D004958:Estradiol / Q000096:biosynthesis; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007377:Interleukin-3 / Q000378:metabolism*; D008297:Male; D016133:Polymerase Chain Reaction; D012016:Reference Values; D012727:Sex Characteristics; D014158:Transcription, Genetic
D017077:Culture Media, Conditioned; D016207:Cytokines; D007377:Interleukin-3; D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases