title: Steroid and growth factor modulation of aromatase activity in MCF7 and T47D breast carcinoma cell lines.
abstract: The effect of a number of steroids, growth factors, and peptides on aromatase activity in two estrogen receptor positive breast cancer cell lines (MCF7 and T47D) was investigated. The cells were incubated in Dulbecco's minimum essential medium containing phenol red and 10% fetal calf serum. Pronounced differences in basal aromatase activity and different responses to the addition of experimental agents were found in the two cell lines. Aromatase activity in MCF7 cells was significantly stimulated by phorbol 12,13-diacetate [PDA], dibutyryl cyclic AMP [(Bu)2cAMP], transforming growth factor alpha, and epidermal growth factor individually and PDA and (Bu)2cAMP in combination, while it was inhibited by dexamethasone and unaffected by transforming growth factor beta, fibroblast growth factor, platelet-derived growth factor, prolactin, and tamoxifen. Addition of cortisol to MCF7 cells had no effect on aromatase activity at 1 nM, caused suppression of activity at 10 nM and stimulated activity at 100 nM. Aromatase activity in T47D cells was stimulated by transforming growth factor alpha, epidermal growth factor, platelet-derived growth factor, prolactin, dexamethasone, and cortisol individually and PDA and (Bu)2cAMP in combination. It was unaffected by transforming growth factor beta, PDA, (Bu)2cAMP, and fibroblast growth factor. These findings suggest that aromatase activity is induced by agents which stimulate cyclic AMP-dependent protein kinases [e.g., (Bu)2cAMP] and that this effect is potentiated by factors which stimulate protein kinase C [e.g., PDA]. The effect on aromatase activity of growth factors, the actions of which are believed to be mediated by receptors linked to tyrosine kinase activity, is not as clearly defined, with a factor causing stimulation, inhibition, and no change in activity depending on the tissue concerned. Further insight into these differences will require resolution of the molecular mechanisms that mediate the actions of stimulatory and repressive growth factors on aromatase activity of oestrogen-producing cells.
authors.affiliation: Department of Academic Biochemistry, Royal Marsden Hospital, London, United Kingdom.
authors.forename: C M
authors.initials: CM
authors.lastname: Ryde
authors.forename: J E
authors.initials: JE
authors.lastname: Nicholls
authors.forename: M
authors.initials: M
authors.lastname: Dowsett
mesh_terms: D001141:Aromatase / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004347:Drug Interactions; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004967:Estrogens / Q000096:biosynthesis*; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D010703:Phorbol Esters / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011388:Prolactin / Q000494:pharmacology; D013256:Steroids / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology; D015291:Transforming Growth Factors / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D004967:Estrogens; D006133:Growth Substances; D010703:Phorbol Esters; D010982:Platelet-Derived Growth Factor; D013256:Steroids; D013629:Tamoxifen; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D003994:Bucladesine; D015291:Transforming Growth Factors; D003907:Dexamethasone; D011388:Prolactin; D001141:Aromatase