Paracrine influence of human breast stromal fibroblasts on breast epithelial cells: secretion of a polypeptide which stimulates reductive 17 beta-oestradiol dehydrogenase activity.
We have previously shown that a stroma-associated paracrine influence may occur in the human breast. In particular, human breast fibroblasts secrete a factor which stimulates reductive 17 beta-oestradiol dehydrogenase (HSD) activity, thereby regulating tissue concentrations of 17 beta-oestradiol. We report here the results of experiments designed to establish the nature of the enzyme activity stimulating factor. In vitro cell culture techniques were used, in which human breast fibroblast-conditioned medium was used to grow the human breast cancer cell line, MCF-7, for 6 days, after which the reductive HSD activity of the monolayers was assessed. The fibroblastic reductive HSD stimulating factor was found to be a trypsin-sensitive polypeptide. The polypeptide eluted from a Sephadex G-75 column as a peak corresponding to a molecular weight of about 50 kDa. The polypeptide exerts its effects by altering the Vmax of 2 of the cytosolic forms of HSD within MCF-7 cells. This is achieved by a protein-synthesis-dependent but calmodulin-independent mechanism. These results provide further evidence of a paracrine effect by stromal tissue within the human breast and have important implications with respect to the aetiology and treatment of breast cancer.
Adams
E F
EF
Department of Chemical Pathology, St. Mary's Hospital Medical School, London, UK.
Newton
C J
CJ
Tait
G H
GH
Braunsberg
H
H
Reed
M J
MJ
James
V H
VH
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D001940:Breast / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D002850:Chromatography, Gel; D003470:Culture Media; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation; D004848:Epithelium / Q000378:metabolism; D004960:Estradiol Dehydrogenases / Q000378:metabolism*; D005260:Female; D006801:Humans; D010455:Peptides / Q000378:metabolism*; D014357:Trypsin
D003470:Culture Media; D010455:Peptides; D015067:17-Hydroxysteroid Dehydrogenases; D004960:Estradiol Dehydrogenases; D014357:Trypsin