Paracrine influence of human breast stromal fibroblasts on breast epithelial cells: Secretion of a polypeptide which stimulates reductive 17β-oestradiol dehydrogenase activity

Autor: C.J. Newton, Michael J. Reed, V.H.T. James, Hannelore Braunsberg, Eric F. Adams, G. H. Tait
Rok vydání: 1988
Předmět:
Zdroj: International Journal of Cancer. 42:119-122
ISSN: 1097-0215
0020-7136
DOI: 10.1002/ijc.2910420122
Popis: 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.
Databáze: OpenAIRE