title: Induction of transforming growth factor beta 1 in human breast cancer in vivo following tamoxifen treatment.
abstract: We have investigated the ability of tamoxifen to regulate members of the transforming growth factor beta (TGF-beta) family in human breast cancers in vivo. Using immunohistochemical techniques, we find that 3 months of tamoxifen treatment causes a consistent induction of extracellular TGF-beta 1 in breast cancer biopsies, compared with matched pretreatment samples from the same patient. The induced TGF-beta is localized between and around stromal fibroblasts and appears to be derived from these cells. Lower levels of TGF-beta 1,-beta 2, and -beta 3 seen in epithelial cells were not altered by tamoxifen treatment. The increased stromal staining of TGF-beta 1 occurred in estrogen receptor-negative as well as estrogen receptor-positive tumors. These results provide in vivo evidence for a novel, estrogen receptor-independent mechanism of action for tamoxifen, involving the stromal induction of a potent growth inhibitor for epithelial cells.
authors.affiliation: Hartwell Laboratory Royal Marsden Hospital, London, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Butta
authors.forename: K
authors.initials: K
authors.lastname: MacLennan
authors.forename: K C
authors.initials: KC
authors.lastname: Flanders
authors.forename: N P
authors.initials: NP
authors.lastname: Sacks
authors.forename: I
authors.initials: I
authors.lastname: Smith
authors.forename: A
authors.initials: A
authors.lastname: McKinna
authors.forename: M
authors.initials: M
authors.lastname: Dowsett
authors.forename: L M
authors.initials: LM
authors.lastname: Wakefield
authors.forename: M B
authors.initials: MB
authors.lastname: Sporn
authors.forename: M
authors.initials: M
authors.lastname: Baum
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D011960:Receptors, Estrogen / Q000032:analysis; D013629:Tamoxifen / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D016212:Transforming Growth Factor beta; D013629:Tamoxifen